Regenerative Medicine: Therapy for the Troubled HeartProf . Simon P. Hoerstrup, MD, PhD (WIEF-AFF Roundtable, May 26th 2015, Tokyo, Japan)

Regeneration – Prometheus Saga

Lakonische Schaleca 530 v. Christus

Principles of Cell-based Therapies
CELLS

SCAFFOLD

IN VITROCULTUREAUTOGENIC

NATURALSTATICALLOGENICSYNTHETICDYNAMICXENOGENIC

BIODEGRADABLEIMPLANTRegenerative Medicine: Therapy for the Troubled Heart

Example I: Tissue Engineered, Living Heart
Valves with Regeneration and Growth Potential

Prof . Simon P. Hoerstrup, MD, PhD (WIEF-AFF Roundtable, May 26th 2015, Tokyo, Japan)

The Evolution of Heart Valve Prostheses
MECHANICAL

1960„BIOLOGICAL“

1990-2000

TISSUE ENGINEERED2010

2015-20

The Native Benchmark
Viable, AutologousRegeneration“Growth“
AntithrombogenicWeber B. et al.
Seminars Immunopathology 2011; 21:307-15

Polymer Scaffold Technologies

Heat welding*Injection molding* HOERSTRUP SP et al. (2000) CIRCULATION 102(III); 44-49

Electro spinning

Rapid
prototyping

Imaging Based Computation
FSI calculations have enabled identification of thedeformations in the heart valve, both in systole and diastolede Hart et al , J. Biomech. (2003)
Baaijens, IJNMF (2001)

Rutten et al (2004)

Pulse Duplicator (Bioreactor) Systems* HOERSTRUP SP et al. (1999) TISSUE ENGINEERING* SODIAN R, HOERSTRUP SP et al. (2002) TIS. ENG.
* MOL A, HOERTRUP SP et al. (2005) ANN BIOMED ENG

Zürich Tissue Engineering Heart Valve Program
Differentiated (Vascular Derived) Cells* HOERSTRUP SP et al. (2000) CIRCULATION 102(III);44-49* HOERSTRUP SP et al. (2006) CIRCULATION 114(I);159-166* MOL A, HOERSTRUP SP et al (2006) CIRCULATION 114 (I) 152-158

Mesenchymal Stem/Progenitor Cells* KADNER A, HOERSTRUP SP et al. (2002) ANNALS THOR SURG 74(4);S1422-8* KADNER A, HOERSTRUP SP et al. (2004) EJCTS 25(4);635-641* HOERSTRUP SP et al. (2002) CIRCULATION 106(I); 143-150* SCHMIDT D, DIJKMAN P, HOERSTRUP SP et al. (2010) JACC 56(6):510-20* WEBER B, HOERTRUP SP et al (2011) EUROPEAN HEART JOURNAL* EMMERT M, HOERSTRUP SP et al (2011) JACC INTERVENT.
* EMMERT M, HOERSTRUP SP et al (2012) JACC INTERVENT.
* EMMERT MY, HOERSTRUP SP et al (2013) EUR J CARDIOTHORACIC SURGERY* EMMERT MY, HOERSTRUP SP et al (2013) JACC (in press)

Blood Derived Stem/Progenitor Cells* SCHMIDT D, HOERSTRUP SP et al. (2004) AHA* SCHMIDT D, HOERSTRUP SP et al. (2004) ANNALS THOR SURG 78;2094-98* SCHMIDT D, HOERSTRUP SP et al (2006) ANNALS THOR SURG 82(4); 1465-71* SCHMIDT D, HOERSTRUP SP et al. (2006) TISSUE ENGINEERINGPrenatal (Placental, Umbilical Blood) Stem Cells* SCHMIDT D, HOERSTRUP SP et al. (2005) EJCTS 27(5);795-800* SCHMIDT D, HOERSTRUP SP et al. (2006) CIRCULATION 114(I); 125-131* SCHMIDT D, HOERSTRUP SP et al. (2007) CIRCULATION 116(11), I64-70* WEBER B, HOERTRUP SP et al (2012) BIOMATERIALS, e-pub ahead

Tissue Engineered Heart Valves (Aortic Position)

LifeValve/Lifematrix - Living autologous heart valves
for minimally invasive implantation procedures

Funding
Swiss National Foundation (SNF, SNF-SPUM), SwisTransMed LifeMatrix; EU Framework Programs (FP6 BioSys, FP7LifeValve, FP7 IMAValve), BMBF Germany, HSM Switzerland, Smartmix TeRM, German Research Foundation

Media Briefing – EU Research & Innovation in HealthcareRegenerative Medicine: Therapy for the Troubled Heart

Example II: Stem Cell based Repair andRegeneration after Heart Attack (MyocardialInfarction)

Prof . Simon P. Hoerstrup, MD, PhD (WIEF-AFF Roundtable, May 26th 2015, Tokyo, Japan)

Center
forReMedi
Regenerative& BiologicallyTherapies (ReMedi)
NCCR– BiologicalMedicine
Mechanisms
in RegenerationInspiredand Repair

Myoardial Infarction: Transcatheter Stem Cell Treatment

M. Y. Emmert, et al, V. Vogel, S.P. Hoerstrup(2013). Biomaterials 34(10): 2428-2441
STRAUER BE et al (2003) CIRCULATION

Center
forReMediRegenerative& Biologically
Therapies (ReMedi)
NCCR– BiologicalMedicine
Mechanisms
in RegenerationInspired
and Repair

Stem Cell-based Microtissues for Myocardial Infarction
catheter-based
intramyocardial
application

Bone Marrow Puncture
MSC culture
VGEF

24 hours

day 4vWF

microtissue size
96 hours

36 hours
3D Microtissue Formation

72 hours

48 hours

additional cell types/labeled cells
M. Emmert, V. Vogel, S.P. Hoerstrup (2013), PloS One, 8(3):e57759
M. Emmert, V. Vogel, S.P. Hoerstrup (2013). Biomaterials 34(10): 2428-2441

microtissue viability

“Last Mile” of Clinical Translation
Classical Academic Research

Wyss Translational Center ZurichTranslational
Infrastructure(GLP&GMP)

Therapy

Bench / Invention

Bedside / ProductProducts

Basic Research

Pre-Clinical Research /Proof-of-Concept

First-in-Man Trials(GCP)

Services

Clinical Translation /Technology Transfer

Clinic /MarketProjects /Studies
1603.08.2015

A Center of ETH Zurich and University of Zurich

Zurich LifeMatrix (Tissue engineered heart structures)
1% of newborns have congenital
heart malformations (absent heartvalves, blood vessels, etc.)
Current therapies are invasive andrequire the use of artificial, non-living
prosthetic material• Limitation in terms of growth andregeneration• Multiple reoperations needed

Autologous, personalized cellulartissues overcome these limitations• Capacity of growth and regeneration• Applicable both in children and adults

LifeMatrix platform aims at First-in-Man studies of novel “off-the-shelf” tissue engineered
homologous matrices
Matrix-On-The-Chip platform (ETH), GMP Clinical Translational Platform (UZH), Clinical Pilot
Study Platform (USZ)

1803.08.2015

A Center of ETH Zurich and University of Zurich

Zurich VAD (Ventricular Assist Devices)
Heart failure (HF) is one of the leading
causes of death in the world• By 2030 > 8m patients will suffer from HF• Clinical costs will reach EUR 30bn inEurope

Current therapies, incl. heart transplantations or artificial VADs,
have limitations:• Shortage of donors• VADs lack performance and reliability

Off-the-shelf artificial device similar
to human heart in terms of sensing,pumping & biocompatibility• Reduction of the need of donor hearts• Replacement of existing VADs

Zurich Heart’s targeted innovations for clinical adoption are, among others, coatings forlong term integration, automatic control algorithms for blood pumps

1903.08.2015

A Center of ETH Zurich and University of Zurich

“Last Mile” of Clinical Translation - PPPClassical Academic Research

Wyss Translational Center ZurichTranslational
Infrastructure(GLP&GMP)

Therapy

Bench / Invention

Bedside / ProductProducts

Basic Research

Pre-Clinical Research /Proof-of-Concept

First-in-Man Trials(GCP)

Services

Clinical Translation /Technology Transfer

Clinic /MarketProjects /Studies
2003.08.2015

A Center of ETH Zurich and University of ZurichRegenerative Medicine: Therapy for the Troubled HeartProf . Simon P. Hoerstrup, MD, PhD (WIEF-AFF Roundtable, May 26th 2015, Tokyo, Japan)

Mechanobiology* SAUREN F et al. (1983) J BIOMECHANICS* SCHOEN FJ et al. (1997) J HEART VALVE DIS