The potential factors regulating endogenous regeneration.
Tao-Sheng Li
Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Japan.
The regeneration of injured tissues/organs is known to be highly depended on not only the “seed =stem/progenitor cells” but also the “soil = tissue microenvironment”. By monitoring the kinetic
changes of cytokines/chemokines and extracellular matrix/adhesion molecules in liver and heart ofmice after experimental injuries, we have tried to find the potential factors regulating endogenous
regeneration of liver and heart. Although our preliminary data suggests that some factors likely
involve in the regenerative process of liver and heart after injury, serious experiments in vitro and invivo are asked for further identification.
Biography:
1991 M.D., Jiangxi Medical College, China.
2000 Ph.D., Yamaguchi University, Japan.
2004 Assistant Professor, Yamaguchi University Graduate School of Medicine, Japan.
2008 Research Scientist, Cedars-Sinai Medical Center, USA.
2011 Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Cell-based therapy with modified mononuclear cells for radiation-damaged salivary glands.
Yoshinori Sumita
Basic & Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate
School of Biomedical Sciences, Japan.
Xerostomia is one of the important complications following the radiotherapy for head and neck cancer.
However, unfortunately, there are no adequate treatments for patients with such irreversible glandular
damages at present. Therefore, our group has recently investigated the cell-based therapies using themodified bone marrow or peripheral blood mononuclear cells. In this presentation, I will show thecurrent progress of our approaches regarding the cell-based therapy for the radiogenic xerostomia.

Biography:
1995 D.D.S., Aichi University, Japan.
2007 Ph.D., Nagoya University, Japan.
2007 Postdoctoral Fellow, Faculty of Dentistry, McGill University, Montreal, Canada.
2009 Assistant Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.
2012 Associate Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.
2015 Adjunct Professor, Faculty of Dentistry, McGill University, Montreal, Canada.

Remodeling the vasculature niche in the decellularized lung scaffold.
Tomoshi Tsuchiya
Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences,Japan.
Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient’s
own cells could provide desperately needed donor organs in the future. However, existing
bioengineered lungs are fragile, in part because of their immature vascular structure. The applicationof adipose-derived stem/stromal cells (ASCs) improved the quality of engineered pulmonary
vasculature via differentiation ability and cytokines secretion; which remodels the vasculature nichein the regenerated lung.

Biography:
1993 M.D., Nagasaki University School of Medicine, Japan.
2002 Ph.D., Nagasaki University Graduate School of Biomedical Sciences, Japan.
2002 Postdoctoral Fellow, University of California, Riverside, USA.
2008 Assistant Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.
2011 Visiting Scientist, Yale University, USA.
2010 Associate Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Regenerative medicine in digestive organ.
Mitsuhisa Takatsuki
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Here, we introduce our inventions of regenerative medicine, mainly utilizing the cell sheet technology
in digestive organ, including esophagus, liver, and islet cells of pancreas.
In clinical esophageal surgery, we have developed to apply the fibroblast cell sheet to prevent thestricture of the esophagus after endoscopic submucosal dissection. In liver and islet cell, we havedemonstrated to achieve functioning cell sheet in animal model, and further trying to develop cellsheet which sufficiently function even under the skin.

Biography:
1994 M.D., Nagasaki University School of Medicine, Japan.
2000 Clinical Fellow, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
2002 Ph.D., Nagasaki University Graduate School of Biomedical Sciences, Japan.
2005 Assistant Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.
2009 Lecturer, Nagasaki University Graduate School of Biomedical Sciences, Japan.
2016 Associate Professor, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Harnessing micro- and nano-technologies for better cell therapies.
Ke Cheng
Department of Molecular Biomedical Sciences, North Carolina State University, USA.
Department of Biomedical Engineering, UNC-Chapel Hill & NC State University, USA.
No therapy currently available can reduce the size of an established scar on the heart. Cell therapy
aims to alter this fixed trajectory for MI survivors: to intervene adverse heart remodeling, to reducescar size, and to actually regenerate viable myocardial tissue. The last one and half decades witnessed
the booming of stem cell therapies for multiple diseases. Our lab has been studying heart-derived
cardiac stem cells (CSCs) in the past 7 years. Efficacy in cell transplantation is hampered by low rates
of cell retention and engraftment in the tissue parenchyma. We have developed multiple
bioengineering strategies to enhance the delivery of stem cells. Also, Stem cells must be carefully
preserved to keep them alive and functioning until the time of transplant, and there are some risks
involved in cell transplantation as well. We have engineered synthetic stem cells to overcome thesebarriers.

Biography:
2004 B.S., Zhejiang University, China.
2008 Ph.D., University of Georgia, USA.
2008 Research Scientist Faculty, Cedars-Sinai Medical Center, USA.
2010 Assistant Professor, Cedars-Sinai Medical Center, USA.
2013 Associate Professor, North Carolina State University, USA.
2016 Adjunct Associate Professor, UNC Eshelman School of Pharmacy, USA.

Exosomes generated from stem cells prevent cardiomyocyte apoptosis in the ischemic
myocardium.
Yaoliang Tang
Department of Medicine, Cardiology, Vascular Biology Center, Medical College of Georgia, USA.
Induced pluripotent stem cells (iPS) exhibit enhanced survival and proliferation in ischemic tissues.
However, the therapeutic application of iPS cells is limited by their tumorigenic potential. We
hypothesized that iPS cells can transmit cytoprotective signals to cardiomyocytes via
exosomes/microvesicles. Exosomes/microvesicles secreted from mouse cardiac fibroblast (CF)derived iPS cells (iPS-exo) were purified from conditioned medium and confirmed by electron
micrograph, size distribution and zeta potential by particle tracking analyzer and protein expressionof the exosome markers CD63 and Tsg101. We observed that exosomes are at low zeta potential, andeasily aggregate. Temperature affects zeta potential (-14 to -15 mV at 23 °C vs -24 mV at 37 °C). The
uptake of iPS-exo protects H9C2 cells against H2O2-induced oxidative stress by inhibiting caspase
3/7 activation (P < 0.05, n = 6). Importantly, iPS-exo treatment can protect against myocardialischemia/reperfusion (MIR) injury via intramyocardial injection into mouse ischemic myocardium
before reperfusion. Furthermore, iPS-exo deliver cardioprotective miRNAs, including nanogregulated miR-21 and HIF-1α-regulated miR-210, to H9C2 cardiomyocytes in vitro. In summary,
Exosomes/microvesicles secreted by iPS cells are very effective at transmitting cytoprotective signals
to cardiomyocytes in the setting of MIR. iPS-exo thus represents novel biological nanoparticles thatoffer the benefits of iPS cell therapy without the risk of tumorigenicity and can potentially serve as
an "off-the-shelf" therapy to rescue ischemic cardiomyocytes in conditions such as MIR.

Biography:
1993 M.D., Shanghai Jiao Tong University, China.
2002 Ph.D., Fudan University, China.
2003 Postdoctoral Fellow, University of South Florida, USA.
2004 Assistant Professor, University of South Florida, USA.
2008 Associate Professor, Keck Graduate Institute, Claremont University Consortium, USA.
2013 Associate Professor, Medical College of Georgia, USA.
2017 Professor (Tenured), Medical College of Georgia, USA.

E2F1 in EPC oxidative metabolism and endothelial differentiation.
Gangjian Qin
Department of Biomedical Engineering, School of Medicine/School of Engineering, The Universityof Alabama at Birmingham, USA.
The majority of current cardiovascular cell-therapy trials use bone marrow progenitor cells (BM PCs)
and achieve only modest efficacy; the limited potential of these cells to differentiate into endotheliallineage cells is one of the major barriers to the success of this promising therapy. We have previously
reported that the E2F transcription factor 1 (E2F1) is a repressor of neovascularization following
ischemic injury, but whether E2F1 regulates BM PC function is unknown. In this study, we found that
ablation of E2F1 (E2F1–/–) in mouse BM PCs increases oxidative metabolism and reduces lactateproduction, resulting in enhanced endothelial differentiation. The metabolic switch in E2F1–/– BM
PCs is mediated by a reduction in the expression of pyruvate dehydrogenase kinase 4 (PDK4) andPDK2; overexpression of PDK4 reverses the enhancement of oxidative metabolism and endothelialdifferentiation. Deletion of E2F1 in the BM increases the amount of PC-derived endothelial cells inthe ischemic myocardium, enhances vascular growth, reduces infarct size, and improves cardiac
function after myocardial infarction. Our results suggest a novel mechanism by which E2F1 mediates
the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 and/or enhanceoxidative metabolism in BM PCs may improve the effectiveness of cell therapy.

Biography:
1989 M.D./M.S., Tongji Medical University, China.
1992 Lecturer, Tongji Medical University, China.
2001 Instructor in Medicine, Tufts University School of Medicine, USA.
2004 Assistant Professor, Tufts University School of Medicine, USA.
2007 Assistant Professor, Northwestern University Feinberg School of Medicine, USA.
2012 Associate Professor, Northwestern University Feinberg School of Medicine, USA.
2016 Professor (Tenured), Director of Molecular Cardiology Program, Vice Chair of Research,
School of Medicine/School of Engineering, The University of Alabama at
Birmingham, USA.

Bmi-1 high-expressing cells enrich cardiac stem cells and respond to heart injury.
Yucai Xie
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,
China.
Bmi-1 gene is well recognized as an oncogene, but has been recently demonstrated to play a role inthe self-renewal of tissue-specific stem cells. By using Bmi-1GFP/+ mice, we investigated the probablerole of Bmi-1 in cardiac stem cells and myocardial repair after myocardial infarction. RT-PCR andflow cytometry analysis indicated that the expression of Bmi-1 was significantly higher in cardiac
side population than the main population from CD45-Ter119-CD31- heart cells. More Sca-1+ cardiac
stem cells were found in Bmi-1 GFPhi subpopulation, and these Bmi-1 GFPhi heart cells showed thepotential of differentiation into SMM+ smooth muscle-like cells and TnT+ cardiomyocyte-like cells
in vitro. Otherwise, myocardial infarction induced a significantly increase (2.7-folds) of Bmi-1 GFPhi
population at one week after infarction. These preliminary data suggests that Bmi-1hi heart cells areenriched in cardiac stem cells and may play a role in myocardial repair.
Biography:
1986 M.D., Bengbu Medical University, China.
2002 Associate Professor, Ruijin Hospital, Shanghai Jiao Tong University, China.
2005 Professor, Ruijin Hospital, Shanghai Jiao Tong University, China.
2010 Ph.D., Joint Program of Stowers Institute for Medical Research, USA and Shanghai Jiao Tong
University School of Medicine, China.
2011 Project Scientist, Cedars-Sinai Medical Center, USA.

Stem cell therapy to prevent heart failure: Repair, Regeneration, Rejuvenation.
Ren-Ke Li
Department of Surgery, Division of Cardiac Surgery at the University of Toronto, Canada.
Heart failure results from cardiomyocyte necrosis after myocardial infarction (MI). The heartachieves limited repair through tissue resident and circulating stem cells post MI. Resident cardiac
stem cells are believed to be a legacy of cardiac development, residing in the myocardium but
retaining the capacity for regeneration in times of injury. We recently found inceptive resident
cardiac stem cells of hematopoietic origin that can independently direct endogenous repair.
Age negatively influences the cardiac environment in transplantation recipients and reduces thecardiac tissue’s functional capacity for effective stem cell transplantation. Whereas the cardiac
environment in a young recipient can recuperate aged stem cells, young stem cells perform
inadequately in aged recipients. This paradox suggests that successful stem cell implantation forcardiac repair depends not only on the regenerative capacity of the stem cells, but also on the proper
myocardial milieu. We demonstrated recently that resident cardiac stem cells of hematopoietic
origin govern cardiac repair. Rejuvenation of aged bone marrow increases regenerative capacity byrestoring this resident cardiac stem cell niche. Cardiac resident stem cells play an important role inrestoration of cardiac function and repair.

Biography:
1978 M.D., Harbin Medical University, China.
1988 M.S., University of Toronto, Canada.
1992 Ph.D., University of Toronto, Canada.
1993 Assistant Professor, University of Toronto, Canada.
2002 Professor (Tenured), University of Toronto, Canada.
2011 Fellow of the Canadian Academy of Health Sciences.

What determines differences in regenerative abilities between mice and newts?
Takashi Takeuchi
Division of Biosignaling, Department of Biomedical Sciences, School of Life Sciences, Faculty ofMedicine, Tottori University, Japan.
Mammals can not regenerate almost all major organs other than the liver, but newts can. Whatdetermines the difference? To answer the question, we have focused on cardiac regeneration andcell cycle regulation of cardiomyocytes. We found that silencing of several genes is necessary forinhibition of cardiac regeneration in mice. The mechanism is currently investigated.

Biography:
1983 B.S., Kyoto University, Japan.
1991 Ph.D., Nagoya University, Japan.
1991 Research Scientist, Mitsubishi Kagaku Institute of Life Sciences, Japan.
2001 Principal Investigator, Mitsubishi Kagaku Institute of Life Sciences, Japan.
2009 Professor, Faculty of Medicine, Tottori University, Japan.
2015 Director, Life Science Speciality, Graduate School of Medical Sciences, Tottori University, Japan.