Consortial partners

The consortium is coordinated by Prof. Dr. Ulrich Martin (Leibniz Research Laboratories for Biotechnology and Artificial Organs, LEBAO) and Prof. Dr. Axel Haverich, both Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG). Further leaders of different subprojects at MHH are PD Dr. Ina Gruh and Dr. Robert Zweigerdt (LEBAO) as well as PD Dr. Serghei Cebotari and Prof. Dr. Samir Sarikouch (HTTG) and Prof. Dr. Ulrike Köhl (ICT). The external partners Prof. Dr. Braun from the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Prof. Dr. Susann Boretius and Prof. Dr. Franz-Josef Kaup from the German Primate Center (DPZ), Prof. Dr. Nils Hoppe from the Centre for Ethics and Law in the Life Sciences (CELLS) of the Leibniz University Hannover (LUH), Dr. Sebastian Knöbel and Dr. Dominik Eckardt from Miltenyi Biotec as well as Dr. Michael Harder from corlife will also contribute significantly to the joint project.

 

The non-human primate experiments are performed at the German Primate Center (DPZ) in Göttingen in close collaboration with their scientists, veterinarians and animal caretakers and under strict obedience of legal requirements and animal welfare. Anesthetic procedures for primates established at the DPZ are applied by an anesthesiologist. Additionally, explanation and preparation of the samples for subsequent methods like electron microscopy, immunohistology of frozen and paraffin-embedded sections and molecular detection methods are well-established and are performed by experts in these fields. Clinically and experimentally involved staff from the Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG) of Hannover Medical School has long-standing experience in transplantation of organs, like lungs or heart, as well as the implantation of bioartificial tissue, like blood vessels or heart valves. Trans- and implantations of tissues are performed routinely in large animal models.

 

 

Participants of the second iCARE meeting in August 2018

 

 

Subprojects

Subproject 1 (MHH: Cebotari, Martin; DPZ, ITEM): Transplantation of genetically enriched human iPSC (hiPSC) derived cardiomyocytes (CMs) in a preclinical model of heart repair (non-human primate)

 

Subproject 2 (MHH: Köhl, Martin; Miltenyi): GMP compliant scale up of iPSC-generation and genetic engineering

 

Subproject 3 (MHH: Köhl, Zweigerdt; Miltenyi): Clinical scale up of iPSC-CM and MSC production

 

Subproject 4 (MHH: Zweigerdt; Miltenyi): Development of techniques for enrichment of hPSC-derived cardiomyocyte subtypes

 

Subproject 5 (MHH: Gruh): Development of a potency assay for iPSCs for clinically applicable

heart repair

 

Subproject 6 (MHH: Haverich, Sarikouch): Development of a treatment protocol for intramyocardial iPSC-CM transplantation

 

Subproject 7 (corlife, CELLS): Development of Marketing Strategies for iCARE from an ethical and legal perspective

 

Subproject C (MHH: Martin, Haverich): Coordination of the iCARE consortium

Publications

Weber N, Kowalski K, Holler T, Radocaj A, Fischer M, Thiemann S, et al. Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform. Stem Cell Reports. 2020(* Authors contributed equaly.).

 

Harder M. Herausforderungen innovativer Gewebemedizin aus unternehmerischer Sicht. In: Gerke S., Taupitz J., Wiesemann C., Kopetzki C., Zimmermann H. (eds) Die klinische Anwendung von humanen induzierten pluripotenten Stammzellen. Veröffentlichungen des Instituts für Deutsches, Europäisches und Internationales Medizinrecht, Gesundheitsrecht und Bioethik der Universitäten Heidelberg und Mannheim, vol 48. Springer, 2020.

 

Machado G. Induzierte pluripotente Stammzellen. Allgemeine arzneimittel- und gesundheitsrechtliche Fragen der klinischen Anwendung. In: Medizinrecht. 2020; 38 (4), S. 263–271.

 

Haase A, Glienke W, Engels L, Gohring G, Esser R, Arseniev L, et al. GMP-compatible manufacturing of three iPS cell lines from human peripheral blood. Stem cell research. 2019;35:101394.

 

Isu G, Morbiducci U, De Nisco G, Kropp C, Marsano A, Deriu MA, et al. Modeling methodology for defining a priori the hydrodynamics of a dynamic suspension bioreactor. Application to human induced pluripotent stem cell culture. J Biomech. 2019.

 

Halloin C, Coffee M, Manstein F, Zweigerdt R. Production of Cardiomyocytes from Human Pluripotent Stem Cells by Bioreactor Technologies. Methods in molecular biology (Clifton, NJ). 2019;1994:55-70.

 

Manstein F, Halloin C, Zweigerdt R. Human Pluripotent Stem Cell Expansion in Stirred Tank Bioreactors. Methods in molecular biology (Clifton, NJ). 2019;1994:79-91.

 

de la Roche J, Angsutararux P, Kempf H, Janan M, Bolesani E, Thiemann S, et al. Comparing human iPSC-cardiomyocytes versus HEK293T cells unveils disease-causing effects of Brugada mutation A735V of NaV1.5 sodium channels. Scientific reports. 2019;9(1):11173.

 

Halloin C, Schwanke K, Lobel W, Franke A, Szepes M, Biswanath S, et al. Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture. Stem Cell Reports. 2019;13(2):366-79.

 

Olmer R, Engels L, Usman A, Menke S, Malik MNH, Pessler F, et al. Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture. Stem Cell Reports. 2018;10(5):1657-72.

 

Ackermann M, Kempf H, Hetzel M, Hesse C, Hashtchin AR, Brinkert K, et al. Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections. Nature communications. 2018; 9(1):5088.

 

Christoffersson J, Meier F, Kempf H, Schwanke K, Coffee M, Beilmann M, et al. A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device. Bioengineering (Basel, Switzerland). 2018;5(2).

 

Koch L, Deiwick A, Franke A, Schwanke K, Haverich A, Zweigerdt R, et al. Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation. Biofabrication. 2018;10(3):035005.

 

Wolling H, Konze SA, Hofer A, Erdmann J, Pich A, Zweigerdt R, et al. Quantitative Secretomics Reveals Extrinsic Signals Involved in Human Pluripotent Stem Cell Cardiomyogenesis. Proteomics. 2018;18(14):e1800102.