National Aeronautics and Space Administration

A Researcher’s Guide to:

Cellular Biology

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This International Space Station (ISS) Researcher’s Guide is published by the NASA 

ISS Program Science Office.

Authors: 

Richard Mains, Sharon Reynolds, Mains Associates, Berkeley, Calif.

Tacey Baker, Wyle Integrated Science & Engineering, NASA’s Johnson Space Center

Kevin Sato, Lockheed Martin/NASA’s Ames Research Center

Executive Editor: Amelia Rai

Technical Editor: Neesha Hosein

Designer: Cory Duke

Cover and back cover: 

a. This photo is a fluorescence microscopy image from a stem cell experiment that examined 

mechanotransduction in stem cell tissue progenitors; actin fibers are red, focal adhesions are 

green. (Image Credit: Eduardo Almeida) 

b. Back Cover: The Bioculture System flight hardware that is used to grow cell culture experiments in 

the ISS. (Image credit: NASA/Dominic Hart)

c. Back Cover: Cardiomyocytes in culture that will be grown in the Bioculture System hardware. 

(Image credit: NASA/Elizabeth Blaber)

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Scientist John Freeman prepares seedlings of the model organism Arabidopsis thaliana for a spaceflight experiment 

examining changes in gene expression. (Image credit: NASA/Dominic Hart)

The mission of the International Space Station Program is to advance 

science and technology research, expand human knowledge, inspire and 

educate the next generation, foster the commercial development of space, 

and demonstrate capabilities to enable future exploration missions beyond 

low-Earth orbit (LEO). This booklet, one of a series of 15 Researcher’s 

Guides to the ISS, has been developed to provide prospective investigators 

with an introduction to ISS capabilities, characteristics, resources, 

processes, lessons learned, and knowledge gained in the general topic 

area of Cellular Biology. 

The Lab is Open

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1. Microgravity, or weightlessness, alters many observable phenomena 

within the physical and life sciences. Systems and processes affected by 

microgravity include surface wetting and interfacial tension, multiphase 

flow and heat transfer, multiphase system dynamics, solidification, and 

fire phenomena and combustion. Microgravity induces a vast array of 

changes in organisms ranging from bacteria to humans, including global 

alterations in gene expression and 3-D aggregation of cells into tissue-like 

architecture.

2. Extreme conditions in the ISS environment include exposure to extreme 

heat and cold cycling, ultra-vacuum, atomic oxygen, and high energy 

radiation. Testing and qualification of materials exposed to these extreme 

conditions have provided data to enable the manufacturing of longlife reliable components used on Earth as well as in the world’s most 

sophisticated satellite and spacecraft components.

3. Low Earth orbit at 51degrees inclination and at a 90-minute orbit 

affords ISS a unique vantage point with an altitude of approximately 240 

miles (400 kilometers) and an orbital path over 90 percent of the Earth’s 

population. 

This can provide improved spatial resolution and variable lighting 

conditions compared to the sun-synchronous orbits of typical Earth 

remote-sensing satellites.

Unique Features of the ISS 

Research Environment

1. Microgravity, or weightlessness, alters many observable phenomena 

within the physical and life sciences. Systems and processes affected by 

microgravity include surface wetting and interfacial tension, multiphase 

flow and heat transfer, multiphase system dynamics, solidification, and 

fire phenomena and combustion. Microgravity induces a vast array of 

changes in organisms ranging from bacteria to humans, including 

global alterations in gene expression and 3-D aggregation of cells into 

tissue-like architecture.

2. Extreme conditions in the ISS space environment include exposure to 

extreme heat and cold cycling, ultra-vacuum, atomic oxygen, and highenergy radiation. Testing and qualification of materials exposed to these 

extreme conditions have provided data to enable the manufacturing of 

long-life reliable components used on Earth as well as in the world’s most 

sophisticated satellite and spacecraft components.

3. Low-Earth orbit at 51 degrees inclination and at a 90-minute orbit 

affords ISS a unique vantage point with an altitude of approximately 240 

miles (400 kilometers) and an orbital path over 90 percent of the Earth’s 

population. This can provide improved spatial resolution and variable 

lighting conditions compared to the sun-synchronous orbits of typical 

Earth remote-sensing satellites.

Unique Features of the ISS 

Research Environment

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Why Use ISS as a Laboratory for Cellular Biology Research: 

Questions and Areas 7

Research Areas 7

Results from Past Research 10

Opportunities for Research on the ISS: 

NASA and Center for the Advancement of Science in Space (CASIS) 16

NASA 16

CASIS 16

Solicitations, Proposals & Funding 17

Facilities for Cellular Biology Experiments on the ISS and 

How to Choose Them 18

Advanced Biological Research System (ABRS) 18

BioCulture System (formerly Cell Culture Module) 19

Biotechnology Specimen Temperature Controller (BSTC) 19

Commercial Generic Bioprocessing Apparatus (CGBA) 20

Multipurpose Facilities 22

Lessons Learned 23

ISS Payload/Experiment Logistics and Operations Scenarios 23

Implementing Optimization Strategies for ISS Operations: 

The BioCulture System 24

The Rotating Wall Vessel (RWV): A Microgravity Model System 26

Developing and Flying Research on the ISS 28

Conducting Space Research: The ISS Environmental Conditions 28

Microgravity 28

Radiation Exposure 28

Ambient Gas Concentrations and Pressure 29

Experiment Accommodation on the ISS 29

Developing Your Space Flight Experiment 30

Principal Investigator (PI) Role and Responsibilities 30

Implementation Team Role and Responsibilities 31

Definition, Documentation and Testing of a Space Flight Experiment 31

Development of Spaceflight Experiment Requirements 31

Science Ground Testing 32

Ground Controls 32

Hardware Biocompatibility Tests 32

Project Integration Tests 32

Conducting a Spaceflight Experiment: Payload Flight Operations 32

Funding Opportunities/Points of Contact 34

Citations 35

Appendices 39

Supplemental Hardware List 39

Acronyms 47

Table of Contents

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The definition of Cellular Biology used for this ISS Research Guide includes cell 

culture, tissue culture and related microbial (single-cell organism) experiments. 

These cell-based studies in microgravity support many areas of basic and applied 

research for space exploration and Earth applications. Such research allows the 

conduct of experiments with many replicates, adaptability to various mission 

scenarios, the ability to automate many processes, and amenability to real-time 

results analysis. Additionally, a number of modeled microgravity methods can be 

used to define and refine flight experiments thereby increasing the probability for a 

successful experiment in space. 

A complementary research guide in this series has been developed titled A Researchers 

Guide to International Space Station Microbial Research that focuses on ISS-relevant 

human host-microbe/toxicology/drug interactions (Castro et al., 2013).

Research Areas

In the last 4 billion years, life has evolved and adapted in response to many physical 

and environmental changes on Earth. However, one key feature, the presence 

of gravity at its acceleration of 9.8 m/sec2 (meter per second squared), has not 

changed. Thus, microgravity on the ISS that is due to the platform’s continuous 

free-fall around Earth offers a unique opportunity for novel discoveries of cellular 

and tissue adaptation. These novel discoveries have applications in understanding 

changes to human health during long-duration spaceflight and to Earth-based 

medicine in the areas of biomedical research, tissue engineering, host-toxin 

interactions, host-pathogen interactions, vaccine development, drug sensitivity 

assays, and drug discovery. Using gravity as a variable enables two broad classes of 

space cell biology research: (a) understanding fundamental mechanisms of life’s 

responses to changes in gravity and (b) using gravity as a tool to advance biological 

applications dependent on in vitro tissue culture and the emerging field of tissue 

engineering.

Why Use ISS as a 

Laboratory for Cellular 

Biology Research: 

Questions and Areas

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Basic cell biology experiments led by the NASA space biology and life sciences 

programs over the last 40 years have resulted in a substantial knowledge base of 

how cellular systems respond to spaceflight. Adaptations have been seen in gene 

expression changes, changes in cellular morphology, locomotion, trans-membrane 

signaling, metabolism, and cell-cell association. Advances in analytical capabilities, 

combined with utilizing gravity as a variable, have resulted in numerous peerreviewed publications from spaceflight experiments. In addition, 3-D cell culture 

systems have been used world-wide to model microgravity and have served as 

valuable preflight experiment models, in-flight experiment controls, and groundbased research capabilities that have resulted in a large body of knowledge (NASA, 

2010; National Research Council [U.S.], 2011; Meyers et al., 2013). 

The ISS National Lab offers a valuable platform and environment for cell biology 

investigations, novel discoveries and innovation in a microgravity environment. 

Areas of opportunity include cellular biology and tissue culture studies, tissue 

engineering research using 3-D tissue models, biopharmaceutical production, hostmicrobe interactions, host-toxicology interactions, and host-drug sensitivity and 

resistance. For the last two opportunities, there is a strong linkage with 3-D tissue 

models and these questions illustrate some overlap between space cell biology and 

microbial research. 

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Subject Area Potential Research Questions 

Cellular Response 

to Microgravity 

and Microgravityinduced Physical 

Force Changes

How do microgravity-induced alterations in cell shape, cell structure, 

function, gene expression, or other alterations contribute to the 

understanding of cell and tissue response to microgravity? 

How can this new information contribute to long-duration spaceflight 

and Earth-based medicine? Specific interest areas are: 

• Cell and microbial replication including genetic and metabolic 

regulation. 

• Eukaryotic cell ability to generate/maintain their internal 

cyto-architecture. 

• Cell division and differentiation; cell-cell interactions and 

communication; intra-cellular signaling. 

• Gene expression/chromosome studies. 

• Immune cell response.

• “Omics” studies.

• Clarification of microgravity effects that are due to decreased 

mass transfer and/or physical force changes on cells.

• The combined spaceflight environment effects on cells of 

microgravity and radiation. 

Tissue Engineering of 3-D Tissue 

Models

How can microgravity be used to improve the growth of 3-D tissue 

models for space-based research and Earth-based research in 

tissue engineering, cancer and regenerative medicine? What are 

the factors for increased microbial biofilm formation and the related 

potential for disease? What kind of ground-based radiation studies 

can be done using 3-D tissue models that simulate chronic spaceflight environmental conditions? 

Host-Microbe 

Interactions

What is the impact of microgravity-induced alterations in the 

interaction of pathogens and beneficial microorganisms with cell and 

tissue models? How can this information be applied to operations 

for long-duration spaceflight and Earth-based medicine?

Host-Toxicology 

Interactions & HostDrug Sensitivity and 

Resistance

What is the impact of the interaction of toxins and drugs with cell 

tissue models? How can that information be applied to operations 

for long-duration spaceflight, Earth-based medicine and commercial 

applications?

Table 1: Opportunities for Cellular Biology Research on the ISS.

Research Questions

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Past spaceflight experiment results indicated that mammalian cells can respond 

with profound shape change, altered gene expression, diminished trans-membrane 

signaling, modified differentiation, increased secondary metabolism, and modified 

tissue morphogenesis. The basis of the changes are thought to be a direct response 

of the cell to the change in gravity or, alternatively, to conditions in the cell culture 

environment created by microgravity. The former could invoke an intrinsic response 

structure within the cell. The latter would implicate the loss of gravity-driven 

convection and the hydrostatic pressure gradient, subsequent changes in mass 

transfer regimes, and the forced shape change as etiologic to the cell response. These 

alternatives pose critical questions in the microgravity sciences with impact on both 

biosciences and human health in space. 

Knowledge of the changes in gene expression in cells facilitates the understanding 

of the basis of changes that occur at the tissue level, in organs, in systems, and 

ultimately the organism itself. This approach supports parallel investigations 

in human health, fundamental biology, and Earth-based biomedical and 

biotechnology research and development. Understanding the response of cells to 

microgravity can reveal underlying mechanisms in cell function that can increase 

fundamental knowledge as well as provide unique opportunities for biotechnology 

and commercial developments. The observations in tissue morphogenesis reinforce 

prospects for the latter. 

Early studies with microbes, i.e., bacteria and fungi, showed that they reached 

higher population densities when grown under microgravity conditions than when 

cultures were grown under similar conditions on the ground. Higher cell density 

is likely due to a more homogeneous distribution of cells in the culture medium, 

unlike the settling of cells that occurs on the ground. These studies also showed 

that spaceflight caused some bacterial species to become more resistant to common 

antibiotics (Klaus and Howard, 2006). Verification of increased virulence was 

confirmed by ground-based studies with mice injected with space-flown bacteria 

(Wilson et al., 2007). 

Recently, a spaceflight experiment found that space-grown cultures of the pathogen 

Salmonella typhimurium were significantly more virulent than comparable cultures 

grown on the ground (Wilson et al., 2007). Ribonucleic acid (RNA) microarray 

analyses revealed changes in the gene expression of over 160 gene transcripts, one 

of which was a cross-species, conserved, RNA-binding, regulator protein, Hfq, 

Results from Past 

Research

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which is involved in RNA transcription. Hfq has been found to play a role in 

microbial virulence of several pathogenic bacteria. These data suggested that Hfq 

can play a critical regulatory role in the spaceflight response of bacteria and the 

observed increased virulence, a result that has profound implications for longduration spaceflight. As astronauts and cosmonauts reside for longer periods in a 

closed environment and use recycled water and air, there is an increased potential 

for microbial contamination that may impact their health, safety and performance. 

Adding to the concern are repeated reports that spaceflight suppresses immune 

function, suggesting that disease agents may be more difficult to treat during and 

following long spaceflights. Space-flown plants have also shown significant levels of 

altered gene expression (Paul et al., 2013 [Salmi and Roux, 2008]). Also, analogous 

to suppressed immune function in animals, alterations in cell wall composition in 

plants subjected to spaceflight could result in increases in the susceptibility of plants 

grown in space to pathogen attack (Ryba-White et al., 2001). 

Spaceflight has been shown to affect a variety of mammalian cell types including 

bone, bone marrow cells, cartilage, and tendons, resulting in reduced matrix 

production or altered matrix composition (Doty et al., 1992, 1999). How 

spaceflight affects bone cells is not well understood. For example, how do cells 

sense and respond to changes in gravity? Some scientists suggest that certain cell 

types, when exposed to microgravity, reduce their activity or metabolism as well 

as the amount of new protein normally produced. This exposure to microgravity 

may affect the mature differentiated cell (final cell type for a specific organ-like 

bone) such that the cell generates a “signal” during spaceflight causing it to enter a 

“resting” phase. Another possibility is that the cell division cycle is delayed so that 

cells simply develop into their differentiated state more slowly than normal. A series 

of spaceflight experiments demonstrated that spaceflight suppresses hematopoietic 

differentiation of macrophages; other experiments showed that bone marrow cell 

differentiation in microgravity using murine primary macrophage cell cultures 

noted phenotypic shifts in the bone marrow cell sub-populations (Chapes et al., 

1999). 

Human renal cell cultures flown in space (Hammond et al., 1999) exhibited a 

genetic response to microgravity that exceeded all expectations. Based on RNA 

microarray analyses of spaceflight cultures compared to ground controls, more 

than 1,600 of 10,000 genes examined showed a change in the space-flown cells. 

Investigators are now beginning to focus on groups of specific genes affected by 

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microgravity. A NASA spinoff of this cell biology research, a rotating wall vessel 

(RWV) bioreactor, was developed to culture cells on the ground in an environment 

that models the free fall that particles undergo in cultures grown in actual 

microgravity. This unique bioreactor spinoff has yielded 25 patents, 19 licenses 

and produced thousands of systems that are now in research labs in universities, 

medical centers, commercial laboratories and the National Institutes of Health 

(Hammond and Hammond, 2001). In addition to the new cell biology knowledge, 

the technology and associated research findings have become part of the testing of 

medicines for cancers, development of transplantable tissues, and the growth of 

microorganisms for the development of vaccines and antibiotics.

A RWV bioreactor system (Figure 14) was successfully flown on the space shuttle 

(STS-70, STS-85 and STS-107) and the Russian Space Station Mir (NASA-Mir 3 

and NASA-Mir 7 missions). The experiment aboard NASA-Mir 3 was a 168-day 

culture of bovine cartilage grown on polyglycolic acid scaffolds. Both the spacegrown and ground control RWV 3-D cultures resulted in cartilage formation that 

was superior to the product of standard 2-D culture techniques (Freed et al., 1997). 

A prostate carcinoma experiment aboard Space Shuttle Columbia on STS-107 was 

aimed at understanding the interaction of prostate cancer cells and stromal cells and 

the potential of stromal cells becoming more inductive, increasing the malignant 

potential of the prostate cancer cells (Wang et al., 2005). Previous work performed 

in modeled microgravity in RWVs demonstrated that prostate carcinoma 3-D 

aggregates using the cell line LNCaP required the presence of prostate stromal 

cells to produce prostate-specific antigen (PSA). LNCaP cells grown alone in 3-D 

lost the ability to produce PSA, even in the presence of androgen. In contrast, 

LNCaP cells grown alone in 2-D produce PSA regardless of the presence of 

the stromal cells, suggesting the 3-D co-cultures produce a cellular architecture 

that’s functionally more aligned with human physiology than the 3-D and 2-D 

monocultures (Zhau et al., 1997). 

The STS-107 spaceflight was a unique opportunity to transfer experimental designs 

in cancer biology from ground-based modeled microgravity to actual microgravity 

to test whether spaceflight would more optimally model the cancer growth, 

differentiation and metastasis that occurs in patients (Wang et al., 2005). The initial 

experiment tested the hypothesis of a reciprocal cellular interaction between prostate 

cancer and bone stromal cells and whether permanent genotype and phenotype 

changes occur as a result of growth in a modeled microgravity 3-D culture condition 

(Wang et al., 2005). While the Space Shuttle Columbia, its crew and experiments 

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were tragically lost, electronic images transmitted to the ground from the onboard 

RWV prior to that were compared to RWV ground controls (Figure 1). Images 

from the flight experiment after six days of growth showed space-grown prostate 

organoids nearly the size of golf balls compared to 3-5 mm aggregates in the ground 

experiment. In previous modeled microgravity RWV-grown tissues, permanent 

genetic and behavior changes were found in the prostate cancer cells when cocultured with prostate stromal cells or bone stromal cells (Rhee et al., 2001). A more 

recent research review suggests that controlled studies in microgravity can improve 

our understanding of the basic role of gravity in cancer cell growth and function and 

provide a novel opportunity for innovation and potentially improving treatment 

options in space and on Earth (Becker and Souza, 2013).

A stationary incubator (Figure 4), the Biotechnology Specimen Temperature 

Controller (BSTC) flew on four space shuttle missions (STS-54, STS-56, STS-62 

and STS-90), one NASA-Mir mission (NASA-Mir 6), and three International Space 

Station missions (Expeditions 3, 4, and 5). Data obtained from the experiment 

aboard STS-90 revealed gene expression changes in human primary renal cortical 

cells. The experiment included a set of ground controls: (a) a RWV, (b) a Teflon bag 

in a 3-g centrifuge, and (c) a static Teflon bag at 1 g, identical to that used in the 

BSTC in orbit. The flight cultures showed that expression of more than 1,600 out 

Figure 1: Images of human prostate and bone stroma cells in the JSC Bioreactor Demonstration System on STS-107 

and ground control experiment: The principal investigator was L. Chung of Emory University (Wang et al., 2005). The top 

row is from the rotating perfused bioreactor aboard shuttle. The bottom row is from the ground-rotating, wall-perfused 

vessel. Experiment elapsed time in hours. Source: NASA.

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of 10,000 genes changed, the RWV showed more than 900 genes changed, and the 

3-g centrifuge showed only five genes changed, relative to the static 1-g Teflon bag 

(Hammond et al., 1999). Additional studies conducted using modeled microgravity 

in RWVs or microgravity on the shuttle or ISS are shown in Table 2.

Cell Type or 

Tissue Model 

Response to Microgravity or 

Modeled Microgravity

Flight or 

GroundBased 

System

Reference

Peripheral Blood 

Lymphocyte Cells 

(PBLs)

• Loss of locomotion in micro-g and 

modeled micro-g

• Activation of PBLs with phytohemagglutinin blunted in modeled 

micro-g 

• Locomotion ability remained intact 

when pre-activated with anti-CD3 

and IL-2 prior to culture in modeled 

micro-g

STS-54 - 

BSTC

STS-56 - 

BSTC

GroundBased 

Model - 

RWV

 (Pellis et al., 

1997)

Colon carcinoma • Micro-g and modeled micro-g 3-D 

cultures showed lower cell proliferation, expression of EGF-R, TGF-α, 

TGF-β than 2-D cultures

• Micro-g 3-D cultures showed 

significantly less apoptosis and 

greater carcinoembryonic antigen 

expression than modeled micro-g 

3-D cultures

STS-70 - 

RWV

STS-85 - 

RWV

(Jessup et 

al., 2000)

Bovine chondrocytes • Micro-g cartilage was less dense 

relative to ground modeled micro-g 

control in an RWV

• Mechanical properties of micro-ggrown constructs were inferior to 

those of Earth-grown constructs

• Implications and applications to 

long-duration human spaceflight, 

and to clinical Earth-based medicine 

during prolonged immobilization and 

reduced mechanical loading

Mir 3 - RWV

GroundBased 

Model - 

RWV

(Freed et al., 

1997)

PC-12 rat pheochromo-cytoma cells

• Long-term serial passaging of cells 

in micro-g

• Large cellular aggregates formed in 

micro-g

Mir 6 - BSTC (Unsworth 

and Lelkes, 

1998)

Table 2. Space Cell Biology Experiment Examples Using Actual Microgravity Culture Systems or Modeled Microgravity Systems in 

Rotating Wall Vessels (RWV). (Note: RWVs can be used in both flight- and ground-based studies.) 

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Cell Type or 

Tissue Model 

Response to Microgravity or Modeled 

Microgravity

Flight or 

GroundBased 

System

Reference

HRCE cells • More than 1,632 gene expression 

changes in micro-g cultures

• 914 gene expression changes in modeled micro-g culture

• 5 gene expression changes during 3-g 

centrifugation

• Results indicate RWV simulates some 

aspects of micro-g but some distinct 

changes in micro-g cultures not observed 

in modeled microgravity

STS-90 - 

BSTC

GroundBased 

Model - 

RWV

(Hammond 

et al., 

1999)

Ovarian carcinoma cellsAntigenic protein can be extracted from 

RNAlaterTM-fixed samples stored in less 

than optimal conditions on ISS

ISS 

Expedition 

3 – BSTC

(Hammond 

et al., 

2005)

Lymphoid tissue • Human lymphoid cultures in micro-g did 

not respond to antigenic or polyclonal 

challenge unless stimulated prior to 

exposure

•Human tissues and cells in modeled 

micro-g RWV cultures did not respond to 

recall antigen or polyclonal activator challenge unless stimulated prior to culture

ISS 

Expedition 

4 - BSTC

GroundBased 

Model - 

RWV 

(Fitzgerald et al., 

2009)

HRCE cells Quantitative proteomic information can be 

acquired from samples stored in less than 

optimal conditions on ISS

ISS 

Expedition 

4 - BSTC

(Hammond 

et al., 

2006)

Host-microbe • Increased virulence and stress resistance 

of modeled micro-g RWV-grown Salmonella enterica Serovar Typhimurium

• Increased virulence and unique gene expression and regulation of S. Typhimurium 

cultured during spaceflight 

• Reproduced finding of increased virulence 

of S. Typhimurium cultured during spaceflight and identified the impact of media 

content on this change

• Increased virulence in micro-g paralleled 

RWV-grown cultures and validated use of 

RWV as a micro-g analog

STS-115

STS-123

GroundBased 

Model - 

RWV

(Nickerson et al., 

2000)

(Wilson et 

al., 2007)

(Wilson et 

al., 2008)

Review article Tissue engineering in micro-g bioreactors 

relevant to space biology and medicine

(Barzegari 

and Saei, 

2012)

Human epithelial 

cells

Gene expression from cultures in orbit, 

before or after infected with S. Typhimurium

CCM

STS-131

Analysis 

continuing

Mouse embryonic stem cells

• Tissue regenerative potential of stem cells 

decreased during micro-g

• Inhibited cell differentiation seen

• Gene expression analysis/bio studies 

ongoing

CCM

STS-131

Analysis 

continuing

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In 2005, the U.S. Destiny module of the ISS was designated the ISS National Lab 

(ISSNL) and is the in-orbit research laboratory primarily used by NASA-sponsored 

investigators but also increasingly by other federal entities and the private sector. 

In 2011, NASA chose the non-profit CASIS to be the sole manager of the ISSNL 

for non-NASA-funded research. Their mission is to maximize its innovative use to 

pursue national priorities in science, technology, engineering and mathematics and 

to expand the U.S. economy. 

NASA

NASA’s selection of research projects is guided by recommendations of the National 

Research Council’s 2011 Decadal Survey Report, “Recapturing a Future for Space 

Exploration: Life and Physical Sciences Research for a New Era” (National Research 

Council [NRC; U.S.], 2011). The NASA-developed “Fundamental Space Biology 

(FSB) Science Plan” provides an implementation strategy and roadmap based on 

NRC recommendations and available flight and fiscal resources (NASA, 2010). 

Extractions of research subject areas and research questions from both of the above 

sources are included in Section 2, Table 1. And content in Section 3, regarding 

results from past research, was extracted in part from the FSB Science Plan for Cell, 

Microbial and Molecular Biology. Information on funding sources for this research 

is provided below in the section on solicitations, proposals and funding. 

CASIS

Another option for flying an experiment is through the Center for the 

Advancement of Science in Space (http://www.iss-casis.org). CASIS is a nonprofit 

organization tasked by the U.S. Congress and NASA with promoting and enabling 

non-NASA research on ISS. CASIS can support all stages of payload development 

(http://www.iss-casis.org/CASISBasics/ForResearchers/SupportServices.aspx) and 

can match principal investigators with Implementation Partners (http://www.

iss-casis.org/CASISBasics/ForResearchers/DirectoryofImplementationPartners.

aspx) who can provide heritage hardware, new flight instrumentation or help to 

accommodate PI-provided payloads. Implementation Partners can collaborate with 

Opportunities for Research 

on the ISS: NASA and 

Center for the Advancement 

of Science in Space (CASIS)

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NASA to help streamline the process of payload development, testing, transport to 

orbit and integration with the ISSNL. 

Solicitations, Proposals & Funding

NASA Research Announcements are managed through the online NASA 

Solicitation and Proposal Integrated Review and Evaluation System (NSPIRES), 

http://nspires.nasaprs.com/external/index.do. This system supports the NASA 

research process from the release of solicitation announcements through the peer 

review and selection processes. 

Additional research announcements can be found at the Center for the 

Advancement of Science in Space, http://www.iss-casis.org/Home.aspx. CASIS also 

encourages unsolicited proposals and sponsors prizes. 

A detailed catalog of previous, current, and proposed experiments, facilities, 

and results, including investigator information, research summaries, operations, 

hardware information, and related publications is available at www.nasa.gov/issscience through the NASA ISS Program Office. Additionally, details pertaining 

to research previously supported by the Space Life and Physical Sciences Research 

and Applications Division of NASA’s Human Exploration and Operations Mission 

Directorate can be located in their Division “Task Book” in a searchable online 

database format at: https://taskbook.nasaprs.com/Publication/welcome.cfm.

Funding sources for research on the ISSNL are available via NASA, CASIS, other 

Federal entities and self-funding by the private sector. NASA will continue to cover 

the cost of onboard operation and maintenance of research payloads and their 

transport to and from the ISS. 

Principal

Investigator

Solicitations

(NSPIRES, 

CASIS)

Peer & 

Technical

Review

Selection

Proposals submitted for NASA’s research opportunities undergo scientific and technical review. Center for the Advancement of 

Science in Space has a similar process that is streamlined to optimize ease of user access to the International Space Station 

National Lab. 

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In general, U.S.-developed ISS facilities fall into three availability categories: 

currently aboard; in development with a targeted launch date; and certified/flown 

on the STS and undergoing re-certification for ISS. NASA can provide access to 

hardware in these categories. A fourth category is facilities or equipment available 

from a commercial source either through NASA, through CASIS or provided 

directly by the developer. Some available and soon-to-be available U.S. facilities 

that support cellular biology research are listed below. A supplemental list with both 

U.S. and international partner facilities is included in the Appendix. 

Advanced Biological Research System (ABRS) 

The ABRS is a single-locker system providing two growth chambers. Each growth 

chamber is a closed system capable of independently controlling temperature, 

illumination and atmospheric composition to grow a variety of organisms including 

microorganisms, plants and small arthropods (insects and spiders).

Facilities for Cellular Biology 

Experiments on the ISS and 

How to Choose Them

Figure 2: The Advanced Biological Research System unit in an International Space Station Expedite the Processing of 

Experiments to Space Station rack at NASA’s Kennedy Space Center. Image courtesy of the Bionetics Corporation.

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BioCulture System (formerly Cell Culture Module)

The BioCulture System is still in development for NASA by Tissue Genesis, Inc. 

(http://tissuegenesis.com) and its functions are profiled in Lessons Learned as an 

example of how STS hardware can be upgraded and additionally automated for 

use on the ISS for longer-duration and sequential experiments. The Cell Culture 

Module shown in Figure 3 was an STS-era system utilized for many cellular biology 

studies (see Table 2). The BioCulture System will be an automated and accessible 

cell culture and experiment system that provides controlled maintenance and 

growth in microgravity. The containment system allows for initiation, intervention, 

and analysis of ongoing experiments on ISS. The primary component is a hollow 

fiber bioreactor that is designed to deliver nutrients and remove waste via multiple, 

tightly packed perfusion fibers. The hollow fiber system is particularly suited for 

microgravity cell culture where nutrient transfer is limited to diffusion. Examples of 

previously flown cells include myoblasts, osteoblasts, fibroblasts, endothelial cells, 

stem cells, muscle cells, and bone cells. Standard laboratory processes such as media 

feeds, waste removal, sample collection, protocol additions, or other additions 

are automated. The system is also designed for glovebox-assisted crew access to 

the removable and disposable fluid compartments, allowing for in-orbit culture 

initiation from frozen stores, and recovery of cells/samples for storage and transport 

in low-temperature freezer systems. The system is reconfigurable and customizable.

Biotechnology Specimen Temperature Controller (BSTC) 

The BSTC is a static tissue culture incubator designed to allow multiple shortterm experiments to be controlled simultaneously. It is a single chamber that 

holds 32 Teflon bags of 15-30 ml each. It can accommodate OptiCellsTM (http://

Figure 3: The Cell Culture Module with Multiple Bioreactor Units.

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 19 5/12/15 
20

www.the-scientist.com/?articles.view/

articleNo/13305/title/Tissue-CulturalRevolution/) and provides a selectable 

thermal environment of +4 to +50°C. 

Air/CO2 mixtures can be provided via 

an external Gas Supply Module (GSM). 

Media exchanges and sampling for offline metabolic analysis, cell sampling, 

and 3-D tissue aggregates for fixation 

is performed manually. The BSTC 

provides TCP/IP Ethernet connection 

for communication with the Expedite 

the Processing of Experiments to the 

Space Station (EXPRESS) Rack interface 

computer. 

Commercial Generic Bioprocessing Apparatus (CGBA) 

The CGBA provides programmable, accurate temperature control—from cold 

stowage to a customizable incubator—for experiments that examine the biophysical 

and biochemical actions of microorganisms in microgravity. CGBA can be used in 

a wide variety of biological studies, such as antibiotic-producing bacteria and cell 

culture studies. It is designed to be installed in the EXPRESS Racks for operation 

on ISS.

The CGBA can be fitted with a number of bioprocessing inserts including: 

• Multiple Orbital Bioreactor with 

Instrumentation and Automated Sampling 

(MOBIAS): MOBIAS consists of stackable 

trays, each of which provides an appropriately 

controlled, sterile sample-processing environment 

with passive gas exchange, automated sampling, 

and waste removal. Each tray contains its own 

array of sample, cultures, medias, waste bags, and 

connectors.

Figure 4: The Biotechnology Specimen Temperature 

Controller.

Figure 5: Multiple Orbital Bioreactor with 

Instrumentation and Automated Sampling. 

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 20 5/12/15 
• The Gas Exchange - Group Activation Packs (GE-GAPs): GE-GAPs have an 

aluminum shell that 

enables heat transfer and a 

gas-permeable membrane 

that covers the openings 

in the wall to allow 

passive gas exchange for 

the experimental samples 

located in the GAPs 

inside BioServe’s fluid 

processing apparatus, a 

piece of hardware similar 

to a small test tube that 

can activate, mix, grow, 

and terminate biological 

experiments.

• BioServe Culture Apparatus (BCA): The BCA 

was developed for biological studies, including 

suspension cell culture and tissue engineering 

studies. The BCA allows for passive gas exchange in 

a sterile environment and can provide growth media, 

sampling and fixation of cultures. The BCA allows 

for thermally controlled or software controlled timecourse sampling.

• Culture Habitat (CHab): The CHab consists of 

six culture chambers, which may be inoculated 

sequentially or concurrently. It provides sample 

fixation or activation, passive gas exchange, 

environmental monitoring sensors, video and still 

imagery, and automated, configurable experiment 

control. The CHab can be used for research with cell 

cultures, microorganisms and viruses.

Figure 6. OptiGAP (left) and Gas Exchange - Group Activation Packs (right).

Figure 7. BioServe Culture Apparatus.

Figure 8. Culture Habitat. 

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22

Multipurpose Facilities

• The Microgravity Science Glovebox (MSG): The MSG was built by the 

European Space Agency (ESA) but is operated 

by NASA and is the largest glovebox flown 

in space. It is located in the U.S. Destiny 

module and provides containment for 

experiments, insuring that small or hazardous 

materials do not escape and float about in the 

cabin. Crew members utilize one or more of 

four gloveports to manipulate materials or 

experiment systems that are transferred inside 

via a special opening. It has a video system and 

data downlink to allow control of enclosed experiments from the ground. 

• Other: Various facilities are available on the ISS relevant to cellular biology 

research including: image processing and downlink systems; microscopes; 

biosample freezers; biosample collection, handling, fixation and storage systems; 

and a portable glovebox. More information on biological research facilities and 

multipurpose facilities is available in the NASA publication “International Space 

Station Facilities: Research in Space 2013 and Beyond,” accessible online at www.

nasa.gov/pdf/739318main_ISS%20Utilization%20Brochure%202012%20

Screenres%203-8-13.pdf. 

Figure 9. Microgravity Science Glovebox. 

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ISS Payload/Experiment Logistics & Operations Scenarios

Discussions of experiment design with knowledgeable implementation partners, ISS 

personnel, and hardware providers are important for the planning of experiments 

and preparation of grant proposals. Additional information and points of contact 

are provided below. Some basic guidelines include: 

• Standard laboratory procedures such as pipetting for fluid transfers must be 

modified for containment purposes. Many payloads use syringes with cannula 

attachments interfaced with needle septa. 

• Scientists requiring cold stowage should define their requirements to ensure 

proper storage of reagents, cell culture stocks, and samples for durations that 

will prevent the loss of viability. Selection of fixatives, chemicals, and other 

reagents are assigned hazard classifications that determine the required levels of 

containment.

• The current path for experiment payloads to reach the ISS is by transfer (turnover) 

to a SpaceX Dragon spacecraft at NASA’s Kennedy Space Center between L-24 

and L-18 hours before launch. The procedure must allow for enough time 

from launch to docking to transfer to the ISS experiment integration site when 

designing an experiment. 

• Dragon is the only transportation capsule that currently returns payloads. The 

need for live biosample return must be carefully considered based on the duration 

of time the live specimens will be in a 1-g environment before turnover back to 

the PI.

• There is limited cold stowage and ambient stowage availability for ascent to and 

descent from the ISS. The General Laboratory Active Cryogenic ISS Experiment 

Refrigerator freezer has a permanent rack location assigned to it within Dragon.

• Overall: The Dragon capsule does not include crew, so manual experiment 

procedures need to be deferred until experiment integration occurs within the ISS. 

Return of biosamples to the PI after re-entry takes approximately 72 hours. 

Lessons Learned

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24

Implementing Optimization Strategies for ISS Operations: The 

BioCulture System

The BioCulture System (Figures 10-13) 

is in development for the ISS. It is under 

construction by Tissue Genesis, Inc. 

who developed the earlier Cell Culture 

Module flown several times on the Space 

Transportation System (STS). The STS 

launched to LEO, stayed in orbit for about 

two weeks and then re-entered and landed on 

a long airport runway. STS experiments and 

research specimens were loaded pre-launch, 

transported to orbit and could be activated 

by onboard crew within a few hours. The ISS 

provides a new opportunity to do extended 

research in a true laboratory environment on 

its semi-permanent orbital platform, but the new payloads and supply replacements 

need to be separately transported there from the ground. Increased research facility 

and experiment automation, as designed for the BioCulture System, will provide 

significant benefits because of the already significant requirements on crew time 

for supporting ISS logistics and maintenance operations as well as the extended 

experiment operations. 

The BioCulture System provides crew access to cellular biology research on station 

through the use of cassette containment that can be opened and then resealed in 

the Microgravity Science Glovebox facility (Figure 9). This access allows for culture 

initiation, replenishment, recovery and improved sample collection and storage. 

The automated experiment functions have been increased and improved including 

forward and reverse perfusion, injections with paired fraction collections, cross 

membrane fixation and additional fluidic control points that increase the number of 

automation options. The media, additives and samples are stored in the individual 

cassette refrigerator compartment to lessen the number of manual operations. This 

feature preserves the media quality and improves the storage of samples collected. 

Additionally, the BioCulture System provides a full range of temperature control 

supporting conventional cell culture models and enables research with bacteria 

and embryos. The individual experiment elements required for execution (pump, 

bioreactor, diverter valves, oxygenator, pre-heat, media reservoir, sample, injection 

and sump) are packaged as a disposable insert. When an experiment is completed, 

Figure 10: The BioCulture System with ten 

independent, removable cassettes.

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 24 5/12/15 
Figure 11: Cassette Assembly.

Figure 13: A Single bioreactor unit removed from a bioculture system cassette.

Figure 12: Removable Gas Supply Assembly.

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26

the one-piece disposable insert is removed and a new disposable insert is added to 

start a new experiment within the BioCulture System. The experiment parameters 

are displayed on an experiment specific secure digital card that travels with the 

disposable insert. 

The Rotating Wall Vessel (RWV) Bioreactor: 

A Microgravity Model System

Although microgravity cannot be created on Earth, some aspects can be effectively 

investigated using a modeled (or analog) microgravity cell culture system previously 

designated the RWV bioreactor. It has been used as a partial model for microgravity 

in many cell culture and tissue engineering studies. Four key principles make 

up the RWV bioreactor design: (a) low hydrodynamic shear, (b) co-location of 

particles with differing sedimentation rates, (c) 3-D spatial freedom, and (d) cells 

are continuously falling at terminal velocity through the culture fluid and not 

sedimenting on a surface. These features provide an environment that is similar to 

some aspects of microgravity, facilitating the development of 3-D tissue models that 

produce the cytoarchitecture and functional markers of in vivo tissues. 

Figure 14: Examples of the rotating-wall vessel bioreactor systems available through Synthecon, Inc., Houston, Texas. 

Disc-shaped cylindrical vessels on the left are 10-ml and 50-ml high-aspect rotating vessels (HARVs) attached to a 

four-place rotator base (horizontal-axis rotation). The cylindrical vessels on the right are 55-ml, 110-ml, and 250-ml 

slow-turning, lateral vessels on top of the power supply positioned as controls (vertical-axis rotation) for the modeled 

microgravity produced by the HARVs on the left. Source: Synthecon, Inc. (http://www.synthecon.com/rotary-cell-culturesystems.html).

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 26 5/12/15 
The RWV has been extensively characterized and used for a wide variety of cell 

and tissue types since the original invention by NASA in the mid to late 1980s 

(Barrila et al., 2010; Barzegari and Saei, 2012; Becker and Souza, 2013; Duray 

et al., 1997; Unsworth and Lelkes, 1998). Details of hardware designs for two 

different incubator-based RWV systems, along with operating procedures were 

previously described (Becker et al., 1993; Schwarz et al., 1992). A slow-turning, 

lateral vessel (STLV) consists of a cylindrical vessel with a concentric silicone 

membrane oxygenator and a high-aspect rotating vessel (HARV) that is a variation 

of the cylindrical design with the silicone membrane oxygenator on one end of the 

cylinder (Figure 14). The reduced cross-sectional thickness of the HARV facilitates 

gas exchange, thereby providing an improved environment for cells and tissue types 

that have higher metabolic requirements. With the vessels completely filled with 

culture media (zero headspace), the media viscously accelerates until both the wall 

and fluid mass are rotating at the same angular rate. This eliminates destructive 

shear gradients associated with the boundary layer and wall effects inherent in 

conventional bioreactors (Schwarz et al., 1992). Cells obey simple kinematics and 

are uniformly suspended in the fluid. Solid-body rotation reduces the shear and 

turbulence normally associated with impeller stirred bioreactors, thereby simulating 

some aspects of microgravity (Dedolph and Dipert, 1971; Tsao et al., 1992). The 

vessel operates with no internal moving parts at an unusually low shear regimen of 

0.2 dyne/cm2 (dyne per square centimeter).

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Conducting Space Research: The ISS Environmental Conditions

Understanding key aspects of the ISS research environment is critical to appropriate 

experiment design. Three important elements of the internal environment are 

profiled below. 

Microgravity

Microgravity on the ISS is typically about one millionth of Earth gravity and is 

effectively an environment of near-weightlessness. But gravitational force is not the 

only one that can be relevant to a biological experiment (DeLombard et al., 2004). 

Disturbances may be caused by vibrations (e.g., pumps, fans, exercise systems) 

and/or transient operational phenomena (e.g., valve operation). The magnitude of 

these impacts on the gravitational environment can range from 0.01 g (briefly for 

a thruster jet) to below one millionth of 1 g (prolonged for atmospheric drag in 

orbit).

For biological experiments, it is important to understand the differences between 

the direct effects of microgravity in which a living system perceives changes in the 

gravitational force directly, and indirect effects in which the system responds not 

to the lack of gravitational force itself, but to changes in the local environment 

induced by the conditions of microgravity. The reduction in gravitational forces on 

biosystems results in decreased buoyancy-driven flows, rates of sedimentation and 

hydrostatic pressure. In general, fluid dynamics are also altered, and there is a near 

absence of convection (National Research Council [U.S.], 2011).

Radiation Exposure 

NASA’s current life sciences goals are focused predominantly on understanding the 

effects of space radiation on humans in space and developing strategies to mitigate 

adverse effects. While there is a large body of existing literature on the effects of low 

linear energy transfer (LET) radiation such as gamma rays and X-rays on biological 

samples, including data from long-term animal studies, clinical studies and others, 

the information on radiation of the kind encountered in space (e.g., protons and 

high-LET radiation such as heavy charged ions) is less well-defined (National 

Research Council [U.S.], 2011).

Crews aboard the space station receive an average of 80 mSv (millisievert, 

measurement for radiation dose) for a six-month stay at solar maximum (the time 

period with the maximum number of sunspots and a maximum solar magnetic 

Developing and Flying 

Research on the ISS

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 28 5/12/15 
field to deflect the particles) and an average of 160 mSv for a six-month stay at solar 

minimum (the opposite condition). Although the type of radiation is different, one 

mSv of space radiation is approximately equivalent to receiving three chest X-rays. 

On Earth, we receive an average of 2 mSv every year from background radiation 

alone.

Ambient Gas Concentrations and Pressure

The air within the ISS is dynamically controlled to be close to the gas 

concentrations and total pressure to our atmosphere on Earth. Nitrogen and 

oxygen are stored in tanks and released automatically based on sensor readings, 

and carbon dioxide is chemically absorbed. 

Experiment Accommodation on the ISS 

Experiment payloads are all held within International Standard Payload Racks 

(ISPRs) within the ISS. Each ISPR consists of an outer shell that provides a set of 

standard interfaces, a support structure and modular equipment for supporting 

research hardware. Each can accommodate one or several experiments. 

Through the ISPRs, the ISS payload experiments can be provided with the 

following ISS resources available on the U.S. laboratory, also known as Destiny:

• Electrical power

• Thermal control

• Command/data/video

• Vacuum exhaust/waste gas

• Gaseous nitrogen

The Expedite the Processing of Experiments to the Space Station (EXPRESS) Rack 

System is available to support small, sub-rack payloads with power, data and cooling 

within an ISPR. EXPRESS racks were designed to accommodate payloads originally 

fitted to shuttle middeck lockers and International Sub-rack Interface Standard 

drawers, allowing previously flown payloads to easily transition to flight on the ISS 

(National Research Council [U.S.], 2011). 

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Developing Your Space Flight Experiment

Several milestones along your experiment development path are described below 

as a NASA-supported process that applies to PIs who are NASA-funded grantees 

(see Section 4 - Opportunities for Research on the ISS, above). However, a similar, 

streamlined process is required for PIs who are not NASA-funded including 

CASIS grantees, other government grantees or self-funded commercial entities. 

In this non-NASA funded case, PIs are considered participants on the CASISmanaged ISSNL, and support is provided to them by CASIS and one or more 

Implementation Partners (http://www.iss-casis.org/CASISBasics/ForResearchers/

DirectoryofImplementationPartners.aspx).

When a proposal is accepted as a spaceflight candidate after undergoing scientific 

and technical review, a flight experiment team is formed, the development cycle is 

initiated, then proceeds in phases. The PI will be supported by an assigned project 

scientist who functions as the advocate and liaison for the PI and assists with the 

experiment development process.

For optimal use of the limited in-orbit resources, experiments may be combined 

where feasible—for example, those requiring similar biospecimens and hardware. 

Such teams will work together to achieve individual objectives within the bounds of 

constrained resources. These teams will be manifested and implemented as a group.

Principal Investigator (PI) Role and Responsibilities

The fundamental role and responsibilities of the experiment PI are:

• Definition of the basic scientific and operational requirements for the experiment.

• Working with the project team to ensure that research objectives are maintained 

during design, development and flight.

• After the experiment has been completed, the PI is required to complete and 

submit the analyzed data and a final report to NASA and to publish the results, as 

appropriate.

• Compliance with all safety training, policies and procedures as required by NASA.

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 30 5/12/15 
Implementation Team Role and Responsibilities

The spaceflight Implementation Team is led by a NASA-provided payload or 

project manager. The team works together to manage and implement the phases of 

the experiment development cycle. The NASA-provided project scientist will work 

directly with the PI throughout this process.

Definition, Documentation and Testing of a 

Space Flight Experiment

The following is representative of the documentation, testing and information that 

will be required.

To complete a successful experiment in microgravity, a detailed analysis and 

definition of the proposed experiment must be done. All requirements for the 

execution of the experiment must be identified and described and a feasibility 

analysis conducted.

Additionally, the required hardware and resource requirements must be identified 

in detail for all phases: preflight, flight, and postflight, including assessment of the 

maturity of experiment and financial resources required for experiment. If needed, 

the design, development and manufacture of experiment-unique hardware will 

be conducted, and experiment hardware interfaces and operations will be verified 

through testing.

The PI will work with the assigned Project Scientist to complete all of the required 

phases for development and flight readiness. A series of reviews of the experiment 

will be conducted, including reviews for safety requirements.

As per NASA life sciences flight experiment management policy, if satisfactory 

results are not obtained during testing, a flight experiment may be deselected and 

perhaps considered for ground research based on peer review; or it may need to be 

cancelled altogether.

Development of Spaceflight Experiment Requirements

The foundation of the spaceflight experiment is the clear definition and 

identification of all aspects of the proposed experiment. It is critical that the PI 

work with the project team in a series of activities that are necessary for developing 

the spaceflight experiment.

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32

Science Ground Testing

The project scientist and the flight experiment team will support the PI in defining 

the types of testing that will be required before flight in order to mitigate risks 

and increase the chance of a successful experiment. These tests would include such 

things as validation of new hardware and practice runs to optimize and streamline 

in-orbit operations. The test results will define requirements, procedures, hardware 

setting and configurations. 

Ground Controls

Proper ground control experiments are essential for successful and scientifically 

sound spaceflight experiments. Conducting ground control experiments:

• Synchronous ground control experiments (housed in flight-type hardware on the 

ground) will be supported at NASA. 

• If appropriate, ground control experiments may be performed on a time delay 

to allow for provision of temperature and other parameters that closely simulate 

actual flight conditions.

• Ground control experiments will be supported by NASA.

Hardware Biocompatibility Tests

Hardware biocompatibility testing is warranted in some cases to ensure that 

biosamples and/or organisms do not encounter unexpected difficulties while housed 

in payload system hardware under the prescribed experimental conditions.

Project Integrated Tests

Integrated testing of expected hardware operations and procedures on the ground 

may be warranted. The appropriate testing will be identified by the experiment 

team in collaboration with the PI.

Conducting a Spaceflight Experiment: 

Payload Flight Operations

Launching and delivering a life sciences experiment to the ISS requires extensive 

preparation in support of the logistics activities. NASA provides laboratories for 

preflight preparation and postflight experiment activities. All of the laboratory 

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 32 5/12/15 
equipment that is needed for pre and postflight experiment processing must be 

identified, and specialized equipment may have to be provided by the PI. The 

assigned NASA project scientist will assist and work directly with the PI to provide 

the necessary information and documentation for flight logistics and operations. 

Contingency planning for launch delays is also part of logistics planning.

Typical preflight activities include launch site facility trial runs for preflight 

experiment preparation and processing, training of astronauts for in-flight 

experiment operations and activities supporting transfer of experiment payload 

elements to the launch area. Additionally, trial runs for postflight experiment 

activities to be conducted in laboratories on the ground upon return of the 

experiment to Earth must be considered. 

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34

NASA research announcements are managed through the NASA Solicitation and 

Proposal Integrated Review and Evaluation System. This Web-based system supports 

NASA research from the release of solicitation announcements through the peer 

review and selection processes (http://nspires.nasaprs.com/external/index.do). 

Additional research announcements can be found at the CASIS website: 

http://www.iss-casis.org/Home.aspx.

Funding Opportunities/

Points of Contact

NP-2015-03-018-JSC Cellular Biology-ISS-mini-book.indd 34 5/12/15 
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C.M., and Nickerson, C.A. (2010). Organotypic 3D cell culture models: using the 

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Barzegari, A., and Saei, A.A. (2012). An update to space biomedical research: tissue 

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Becker, J.L., and Souza, G.R. (2013). Using space-based investigations to inform 

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Becker, J.L., Prewett, T.L., Spaulding, G.F., and Goodwin, T.J. (1993). Threedimensional growth and differentiation of ovarian tumor cell line in high aspect 

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Castro, S., Smith, D., and Ott, C. (2013). A researcher’s guide to: International 

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Chapes, S.K., Simske, S.J., Forsman, A.D., Bateman, T.A., and Zimmerman, R.J. 

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Dedolph, R.R., and Dipert, M.H. (1971). The physical basis of gravity stimulus 

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DeLombard, R., Hrovat, K., Kelly, E., and McPherson, K. (2004). Microgravity 

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Doty, S.B., Stiner, D., and Telford, W.G. (1999). The effect of spaceflight on 

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Duray, P.H., Hatfill, S.J., and Pellis, N.R. (1997). Tissue culture in microgravity. 

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Fitzgerald, W., Chen, S., Walz, C., Zimmerberg, J., Margolis, L., and Grivel, J.-

C. (2009). Immune suppression of human lymphoid tissues and cells in rotating 

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Freed, L.E., Langer, R., Martin, I., Pellis, N.R., and Vunjak-Novakovic, G. (1997). 

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Hammond, T.G., and Hammond, J.M. (2001). Optimized suspension culture: the 

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Hammond, D.K., Elliott, T.F., Holubec, K., Baker, T.L., Allen, P.L., Hammond, 

T.G., and Love, J.E. (2006). Proteomic retrieval from nucleic acid depleted spaceflown human cells. Gravitational Space Biol. Bull. Publ. Am. Soc. Gravitational 

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Hammond, T.G., Lewis, F.C., Goodwin, T.J., Linnehan, R.M., Wolf, D.A., Hire, 

K.P., Campbell, W.C., Benes, E., O’Reilly, K.C., Globus, R.K., et al. (1999). Gene 

expression in space. Nat. Med. 5, 359.

Jessup, J.M., Frantz, M., Sonmez-Alpan, E., Locker, J., Skena, K., Waller, H., 

Battle, P., Nachman, A., Bhatti, Weber, M.E., et al. (2000). Microgravity culture 

reduces apoptosis and increases the differentiation of a human colorectal carcinoma 

cell line. In Vitro Cell. Dev. Biol. Anim. 36, 367-373.

Klaus, D.M., and Howard, H.N. (2006). Antibiotic efficacy and microbial 

virulence during space flight. Trends Biotechnol. 24, 131-136.

Meyers, V., Almeida, E., Elliott, T., Landford, S., and Baker, T. (2013). Expert 

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Nickerson, C.A., Ott, C.M., Mister, S.J., Morrow, B.J., Burns-Keliher, L., and 

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Paul, A.-L., Zupanska, A.K., Schultz, E.R., and Ferl, R.J. (2013). Organ-specific 

remodeling of the Arabidopsis transcriptome in response to spaceflight. BMC Plant 

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Pellis, N.R., Goodwin, T.J., Risin, D., McIntyre, B.W., Pizzini, R.P., Cooper, D., 

Baker, T.L., and Spaulding, G.F. (1997). Changes in gravity inhibit lymphocyte 

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Rhee, H.W., Zhau, H.E., Pathak, S., Multani, A.S., Pennanen, S., Visakorpi, T., 

and Chung, L.W. (2001). Permanent phenotypic and genotypic changes of prostate 

cancer cells cultured in a three-dimensional rotating-wall vessel. In Vitro Cell. Dev. 

Biol. Anim. 37, 127-140.

Ryba-White, M., Nedukha, O., Hilaire, E., Guikema, J.A., Kordyum, E., and 

Leach, J.E. (2001). Growth in microgravity increases susceptibility of soybean to a 

fungal pathogen. Plant Cell Physiol. 42, 657-664.

Salmi, M.L., and Roux, S.J. (2008). Gene expression changes induced by space 

flight in single-cells of the fern Ceratopteris richardii. Planta 229, 151-159.

Schwarz, R.P., Goodwin, T.J., and Wolf, D.A. (1992). Cell culture for threedimensional modeling in rotating-wall vessels: an application of simulated 

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Cult. Proced. 14, 51-57.

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Wang, R., Xu, J., Juliette, L., Castilleja, A., Love, J., Sung, S.-Y., Zhau, H.E., 

Goodwin, T.J., and Chung, L.W.K. (2005). Three-dimensional co-culture models 

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Appendices

Supplemental Hardware List

This list, provided for general information purposes, includes both U.S. and 

international hardware, arranged by type (stand-alone incubator systems with an 

associated centrifuge; stand-alone incubator systems with no centrifuge; and tissue 

culture systems requiring the ISS incubator). Cellular biology research facilities 

potentially available for ISS fall into three general categories: currently certified 

for ISS (www.nasa.gov/pdf/739318main_ISS%20Utilization%20Brochure%20

2012%20Screenres%203-8-13.pdf); in development for ISS; and certified/flown 

on STS with potential for re-certification for ISS. This information is meant to 

describe some top-level hardware capabilities and status for each system. 

NASA approval is needed in order to utilize any non-NASA flight hardware listed 

below since access to such items is often based on international agreements and 

hardware utilization exchanges.

Stand-alone Incubator System with an Associated Centrifuge

Cell Biology Experiment Facility (CBEF; Saibo; JAXA)

o Incubator

• Temperature settings: +15°C to +40°C (in 0.1°C increments).

• CO2

 Settings: 0 to 10 percent (in 0.1-percent increments).

• Humidity settings: 20 to 80 percent (in 1-percent increments; dependent on 

the humidity outside of the CBEF).

• Quantity of Biological Experiment Units (BEUs): six; capable of canister 

heating.

• Provides power, sensor data, commanding, and analog video.

o Centrifuge

• Same environmental system as the Incubator.

• Gravity: 0.1 g to 2 g at 112.5-mm radius point; 20 rpm to 140 rpm in 1 

rpm steps

• Quantity of BEUs: four; no canister heating capability.

• Provides power, sensor data, commanding, and analog video.

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o User Interface for a BEU

• Power DC +5 V, -5 V, +12 V, -12 V: one line each.

• Sensor Output 0 V to 5 V.

• Command 1 bit: two lines.

• Standard JEM Video Specifications.

• Shield GND.

o BEU for CBEF Utilization

• Shell for housing User-developed science equipment. 

• Standard user interfaces to the incubator and centrifuge.

• 210 mm by 80 mm by 130 mm (L X W X H).

• Installed with the 80 mm by 130 mm face connected to the incubator or 

centrifuge turntable.

• Centrifugal force vector is parallel to the 210-mm length.

o CEU

• 10 cm2 (3 ml) and 30 cm2 (9 ml) culture chambers.

• Two chambers per CEU.

• Supports adherent tissue culture cell lines.

• 210 mm by 80 mm by 130 mm.

• Medium circulation pump for the sterile, closed fluid loop.

• Fresh Medium Container (25 ml minimum to 80 ml maximum).

• Spent Medium Container.

• Temperature and Humidity Sensors.

• 10-day mission duration, cell processing is postflight only.

o CEU2

• 3 mm by 3 mm by 60 mm culture chambers.

• Two chambers per CEU, fully independent

• Supports non-adherent tissue culture cell lines.

• 290 mm by 80 mm by 130 mm.

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• Medium circulation pump for fluid loops; flow valves.

• Fresh Medium Container (50 ml) and Spent Medium Container.

• Temperature and humidity sensors.

• Automated sampling/fixation (1.5 ml; nine bags per chamber); sampling/

fixation system is detachable for stowage.

• CCD camera with illumination laser, video data downlink.

Biolab (ESA)

o The Incubator houses two centrifuges; all of the Experiment Cassettes (EC) 

are installed on one or both of the centrifuges.

o Incubator Chamber

• Temperature settings: +18°C to +40°C.

• CO2 settings: 0 to 0.0 to 0.2 percent (in 0.01-percent increments); 2 to 5.5 

percent (in 0.1-percent increments).

• O2 settings: 15 to 22 percent (in 1-percent increments).

• Relative Humidity Settings: 60 to 90 percent (in 1-percent increments).

o Centrifuge

• Two independently controlled centrifuges.

• Gravity settings: 0.001 g to 2 g; Radial acceleration at center of EC can be 

selected in 40 steps.

• Six EC per centrifuge.

• Provides power, data, sensor data, video.

• Lighting and video system.

• Provides a liquid handling mechanism for delivering and withdrawing 

fluids.

o EC for the Biolab Incubator

• Shell for user-developed experiment hardware.

• Provides interfaces to the Biolab life support system, power, data, external 

light, fluid handling mechanism, etc.

• Clear cover for use with the external lighting and video system.

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• Available volumes: 60 mm by 60 mm by 100 mm.

• Six ECs per rotor.

• In development: Advanced EC-2.5 liter volume and video connections; two 

per rotor.

Kubik (ESA)

o Two versions: Amber (centrifuge insert) and Topaz (no centrifuge).

o External dimension: 366 mm by 366 mm by 366 mm.

o Internal dimension: 260 mm by 260 mm by 138 mm.

o Amber holds 16 standard Type 1 containers (static) and eight standard Type 1 

containers on the centrifuge.

o Topaz holds up to 40 standard Type 1 containers, all static.

o Temperature settings: +6°C to +38°C (in increments of 1°C).

o Gravity settings: 0.2 g to 2 g (in increments of 0.1 g).

o No atmospheric control.

o No power connectors.

o No data, commanding, or video interfaces.

o Flown on Soyuz and ISS in the Russian Module.

Stand-alone Incubator System with No Centrifuge

Cell Culture Module (CCM; WRAIR; TGI) - Now Evolving to the ISS 

BioCulture System

o Hollow Fiber Bioreactors (max of 24 [3] ml or max of 16 [7] ml bioreactors); 

Custom bioreactor accommodated, mix types in CCM.

o Supports adherent cells, non-adherent, and 3-D tissue culture.

o Temperature Settings: +4°C to +39°C.

o Humidity: Ambient in Module.

o CO2

 control: 5 percent.

o Fluid loops and oxygenator system for CO2 gas exchange perfusion system.

o Fluid/Medium delivery rate can be user-defined.

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o User defined medium bags, fixative bags, and sampling bags need.

o Sensor (temp, CO2) data collection and downlink capable.

o Automated sampling and injection.

o Flown on shuttle (18 flights), must be ISS-certified, CCM-A, B, and C.

Rotating Wall Perfusion System (RWPS; NASA JSC)

o 125-ml rotating wall reactor vessel; one vessel.

o 3-D cell/tissue culture.

o Continuous gas perfusion system; automated medium circulation.

o Three 2-liter fresh medium bags and three 2-liter spent medium bags; medium 

stowage tray holds seventeen 1-liter concentrated medium bags, which are 

diluted prior to use.

o Controllable rotation rate.

o Supports 3-D cultures up to 120 days.

o Temperature setting: +36°C.

o Humidity: passive.

o CO2 control: uses the accessory GSM.

o Manual sampling.

o No previous flights; requires ISS flight certification.

Advanced Separations (ADSEP; TechSHOT)

o CellCult system: 50 ml culture container, perfusion system, fluid loops, 

automated sampling and injection; three CellCult Cassettes per incubator.

o Supports non-adherent.

o Temperature settings: +4°C to +39°C (independent for each cassette).

o Humidity: ambient in module.

o CO2

 control: ambient in module.

o Flown on shuttle only, requires ISS-certification.

EDU-1R (NASA JSC)

o125 ml rotating wall reactor vessel; one vessel.

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o Non-adherent cultures; adherent cultures on microcarrier beads.

o Gas perfusion system; automated medium circulation.

o Supports cultures up to 20 days (gas cylinder volume dependent).

o Pre-programmed medium feeding schedule.

o Differential rotation of the inner and outer cylinders; controllable rotation 

rate.

o Temperature setting: +30°C to +45°C.

o Humidity: passive.

o CO2 control: ses the accessory GSM.

o Manual sampling.

o Previously flown on ISS; requires ISS-certification.

Automated Rotating Culture System (ARCS; NASA JSC)

o Rotating wall reactor vessel; one vessel.

o Supports cultures up to 20 days (internal system) or longer (GSM).

o Intermediate to large scale 3-D cultures and cell aggregates.

o Gas perfusion system, automated medium circulation.

o Pre-programmed medium feeding schedule.

o Medium aeration, medium infusion, and reactor vessel imaging.

o Temperature setting: +30°C to +45°C.

o Humidity: passive.

o CO2

 control: internal system and accessory GSM.

o pH monitoring and control. 

o Manual sampling.

o Prototype.

Tissue Culture Systems Requiring ISS Incubator

Multiple Orbital Bioreactor with Instrumentation and Automated Sampling 

(MOBIAS; BioServe)

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o Gas-permeable bags.

o Supports non-adherent cells and 3-D tissue culture.

o Two temperature zones: +10°C to +37°C to +4°C to +37°C.

o Humidity: ambient in module.

o CO2 control: ambient in module.

o Stacked trays; each tray with medium and waste bag, fluid circulation loops, 

incubation zone, cold/incubation zone, up to 50 ml culture volume (one bag 

or multiple bags), video card, motor drive card, fully automated.

o Incubator required for power.

o Previous shuttle flights, BioServe has indicated it is ISS-certifying all of its 

flight hardware; no crew access to incubation chamber.

Single Loop Cell Culture (BioServe)

o Adherent and non-adherent.

o 10-ml cell culture volume.

o Continuous perfusion of medium for gas exchange.

o Six 3-ml containers for inoculums or samples.

o Automated inoculation or sampling per a pre-set time sequence.

o Fixatives pre-loaded in sampling containers.

o Fresh medium bag waste bag.

o Provides temperature and humidity data.

o Requires power and thermal conditioning from an incubator.

o Requires ISS certification.

Fluid Processing Apparatus (BioServe)

o Non-adherent, previously used for primary and tissue cultured cells.

o Variable volume.

o No medium change out, pre-filled preflight.

o With and without gas exchange membrane.

o Manual or automated injection of secondary solutions.

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o Flown on ISS provides temperature and humidity data.

o Can be used with the Group Activation Pack (BioServe).

o Uses CGBA (BioServe).

BioServe Culture Apparatus (BCA; BioServe)

o Gas permeable bags (4 bags total; 32 ml per bag).

o Syringe system for injections.

o Variable volume.

o Four (5 ml) vacutainers for sample collection.

o Can charge sealed GAP with required gas mixture or use ambient Module air 

(GE-GAP).

o No gas exchange; a version does exist that allows gas exchange, but BioServe 

does not advertise its use anymore.

o Fully automated system.

o ISS certified.

o Uses CGBA (BioServe).

GAP-Derived Cell Culture (BioServe)

o OptiGAP used to house OptiCellsTM; can use the GAP hand pump system 

for injections.

o GE-GAP (gas exchange); gas exchange member in GAP housing.

o ISS certified.

o Uses CGBA (BioServe).

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3-D Three-dimensional 

ABRS Advanced Biological Research System

BCA BioServe Culture Apparatus 

BSTC Biotechnology Specimen Temperature Controller

CASIS Center for Science in Space

CBEF Cell Biology Experiment Facility

CCM Cell Culture Module

CEU Cell Experiment Unit

CGBA Commercial Generic Bioprocessing Apparatus

CHab Culture Habitat

EET Experiment elapsed time

ESA European Space Agency

EXPRESS Expedite the Processing of Experiments to the Space Station

FSB Fundamental Space Biology

GAP Group Activation Pack

GE-GAPS Gas Exchange - Group Activation Packs

GSM Gas Supply Module

HARV High-aspect rotating vessel

ISPR International Standard Payload Rack

ISS International Space Station

ISSNL ISS National Lab

LEO Low-Earth orbit

LET Linear energy transfer

MOBIAS Multiple Orbital Bioreactor with Instrumentation and Automated Sampling

MSG Microgravity Scientific Glovebox

NASA National Aeronautics and Space Administration

NRC National Research Council

NSPIRES Solicitation and Proposal Integrated Review and Evaluation System

PBLs Peripheral blood lymphocyte cells

PI Principal investigator

PSA Prostate-specific antigen

RNA Ribonucleic acid

RWV Rotating wall vessel

STLV Slow-turning lateral vessel

STS Space Transportation System (space shuttle)

Acronyms

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The Complete ISS Researcher’s 

Guide Series

1. Acceleration Environment

2. Cellular Biology

3. Combustion Science

4. Earth Observations

5. Fluid Physics

6. Fruit Fly Research

7. Fundamental Physics

8. Human Research

9. Macromolecular Crystal Growth

10. Microbial Research

11. Microgravity Materials Research

12. Plant Science

13. Rodent Research

14. Space Environmental Effects

15. Technology Demonstration

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For more information...

Space Station Science

http://www.nasa.gov/iss-science

Facilities

http://www.nasa.gov/mission_pages/station/research/

facilities_category.html

ISS Interactive Reference Guide

http://www.nasa.gov/externalflash/ISSRG/index.htm

Researchers/Opportunities

http://www.nasa.gov/mission_pages/station/research/

ops/research_information.html

ISS Research Customer Helpline

JSC-ISS-research-helpline@mail.nasa.gov

281-244-6187

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National Aeronautics and Space Administration

Johnson Space Center

http://www.nasa.gov/centers/johnson

www.nasa.gov

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