Myocardial Tissue Engineering

Objectives

The RG Myocardial Tissue Engineering aims at the establishment and characterization of bio-artificial cardiac tissues (BCTs) for future therapeutic applications. Currently, cardiac cells derived from the different stem cell types are analyzed for their potential to form functional cardiac tissues in combination with collagen based matrices. Functionality of these tissues is tested in a custom made bioreactor system, with a focus on contractility (frequency and force) and viability of the tissue.

Research Focus

One focus of our group is on different technological and mechanistic aspects of stem and progenitor cell biology. We have identified technical artefacts in analysing stem cell differentiation in coculture systems. Based on our work in lentiviral vector technology, we have developed vectors mediating cardiomyocyte-specific reporter gene expression. In the LEBAO, differentiation of murine and primate ESCs and iPS cells into mesendodermal cells and functional cardiomyocytes was demonstrated. Isolation, expansion and differentiation of adult resident cardiac stem cells are also investigated within this JRG. Differentiated cardiac cells are used to generate bioartificial cardiac tissues. Another specific aim of our JRG is the further development of a custom made bioreactor system, for tissue analysis and maturation. We are also focusing on the development of biocompatible matrices to generate surgically implantable tissue for the replacement of scar tissue or the reconstruction of congenital malformations.

Collaborations

A) within REBIRTH:

Further Research Projects

BMBF-Consortium: „Autologous Heart Tisue for Myocardial Repair“, subproject title „Induced pluripotent stem cells for cardiac repair“. BMBF, FKZ 01GN0520. BMBF “Integrated Research and Treatment Center Transplantation” (IFB-Tx), subproject title “Intramyocardial transplantation of adult stem cells for postinfarct myocardial regeneration during CABG surgery – establishment of GMP-conform culture protocols with respect to subsequent conduction of a phase I clinical trial.”

Teaching

  • PhD program Regenerative Sciences
  • Lectures for MHH master class 'Biomedicine' & 'Biochemistry'

Publications

2013 - ongoing

2017

Reboll MR, Korf-Klingebiel M, Klede S, Polten F, Brinkmann E, Reimann I, Schonfeld HJ, Bobadilla M, Faix J, Kensah G, Gruh I, Klintschar M, Gaestel M, Niessen HW, Pich A, Bauersachs J, Gogos JA, Wang Y, Wollert KC. EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction. Circulation. 2017/09/22 ed2017. p. 1809-23.

Rojas SV, Kensah G, Rotaermel A, Baraki H, Kutschka I, Zweigerdt R, Martin U, Haverich A, Gruh I, Martens A. Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction. PLoS One. 2017/05/12 ed2017. p. e0173222.

2016

Dibbert N, Krause A, Rios-Camacho JC, Gruh I, Kirschning A, Drager G. A Synthetic Toolbox for the In Situ Formation of Functionalized Homo- and Heteropolysaccharide-Based Hydrogel Libraries. Chemistry. 2016;22(52):18777-86.

2015

Lachmann N, Brennig S, Hillje R, Schermeier H, Phaltane R, Dahlmann J, Gruh I, Heinz N, Schiedlmeier B, Baum C, Moritz T. Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy. Gene therapy. 2015;22(11):883-92.

Lachmann N, Brennig S, Hillje R, Schermeier H, Phaltane R, Dahlmann J, Gruh I, Heinz N, Schiedlmeier B, Baum C, Moritz T. Tightly Regulated 'All-in-One' Lentiviral Vectors for Protection of Human Hematopoietic Cells from Anticancer Chemotherapy. Gene Ther. 2015;22(11):883-92. Epub 2015/07/01.

2014

Zweigerdt R, Gruh I, Martin U. Your Heart on a Chip: Ipsc-Based Modeling of Barth-Syndrome-Associated Cardiomyopathy. Cell Stem Cell. 2014;15(1):9-11.

Vukadinovic-Nikolic Z, Andree B, Dorfman SE, Pflaum M, Horvath T, Lux M, Venturini L, Bar A, Kensah G, Lara AR, Tudorache I, Cebotari S, Hilfiker-Kleiner D, Haverich A, Hilfiker A. Generation of Bioartificial Heart Tissue by Combining a Three-Dimensional Gel-Based Cardiac Construct with Decellularized Small Intestinal Submucosa. Tissue Eng Part A. 2014;20(3-4):799-809.

Lachmann N, Happle C, Ackermann M, Luttge D, Wetzke M, Merkert S, Hetzel M, Kensah G, Jara-Avaca M, Mucci A, Skuljec J, Dittrich AM, Pfaff N, Brennig S, Schambach A, Steinemann D, Gohring G, Cantz T, Martin U, Schwerk N, Hansen G, Moritz T. Gene Correction of Human Induced Pluripotent Stem Cells Repairs the Cellular Phenotype in Pulmonary Alveolar Proteinosis. Am J Respir Crit Care Med. 2014;189(2):167-82.

Kempf H, Olmer R, Kropp C, Ruckert M, Jara-Avaca M, Robles-Diaz D, Franke A, Elliott DA, Wojciechowski D, Fischer M, Roa Lara A, Kensah G, Gruh I, Haverich A, Martin U, Zweigerdt R. Controlling Expansion and Cardiomyogenic Differentiation of Human Pluripotent Stem Cells in Scalable Suspension Culture. Stem Cell Reports. 2014;3(6):1132-46.

2013

Lachmann N, Brennig S, Pfaff N, Schermeier H, Dahlmann J, Phaltane R, Gruh I, Modlich U, Schambach A, Baum C, Moritz T. Efficient in Vivo Regulation of Cytidine Deaminase Expression in the Haematopoietic System Using a Doxycycline-Inducible Lentiviral Vector System. Gene Ther. 2013;20(3):298-307.

Kensah G, Roa Lara A, Dahlmann J, Zweigerdt R, Schwanke K, Hegermann J, Skvorc D, Gawol A, Azizian A, Wagner S, Maier LS, Krause A, Drager G, Ochs M, Haverich A, Gruh I, Martin U. Murine and Human Pluripotent Stem Cell-Derived Cardiac Bodies Form Contractile Myocardial Tissue in Vitro. Eur Heart J. 2013;34(15):1134-46.

Emmert MY, Emmert LS, Martens A, Ismail I, Schmidt-Richter I, Gawol A, Seifert B, Haverich A, Martin U, Gruh I. Higher Frequencies of Bcrp+ Cardiac Resident Cells in Ischaemic Human Myocardium. Eur Heart J. 2013;34(36):2830-8.

Dahlmann J, Krause A, Moller L, Kensah G, Mowes M, Diekmann A, Martin U, Kirschning A, Gruh I, Drager G. Fully Defined in Situ Cross-Linkable Alginate and Hyaluronic Acid Hydrogels for Myocardial Tissue Engineering. Biomaterials. 2013;34(4):940-51.

Dahlmann J, Kensah G, Kempf H, Skvorc D, Gawol A, Elliott DA, Drager G, Zweigerdt R, Martin U, Gruh I. The Use of Agarose Microwells for Scalable Embryoid Body Formation and Cardiac Differentiation of Human and Murine Pluripotent Stem Cells. Biomaterials. 2013;34(10):2463-71.

2006 - 2012

2011

Moller L, Krause A, Dahlmann J, Gruh I, Kirschning A, Drager G. Preparation and Evaluation of Hydrogel-Composites from Methacrylated Hyaluronic Acid, Alginate, and Gelatin for Tissue Engineering. Int J Artif Organs. 2011;34(2):93-102.

Martens A, Gruh I, Dimitroulis D, Rojas SV, Schmidt-Richter I, Rathert C, Khaladj N, Gawol A, Chikobava MG, Martin U, Haverich A, Kutschka I. Rhesus Monkey Cardiosphere-Derived Cells for Myocardial Restoration. Cytotherapy. 2011;13(7):864-72.

Kuetemeyer K, Kensah G, Heidrich M, Meyer H, Martin U, Gruh I, Heisterkamp A. Two-Photon Induced Collagen Cross-Linking in Bioartificial Cardiac Tissue. Opt Express. 2011;19(17):15996-6007.

Kensah G, Gruh I, Viering J, Schumann H, Dahlmann J, Meyer H, Skvorc D, Bar A, Akhyari P, Heisterkamp A, Haverich A, Martin U. A Novel Miniaturized Multimodal Bioreactor for Continuous in Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation. Tissue Eng Part C Methods. 2011;17(4):463-73.

2009

Haase A, Olmer R, Schwanke K, Wunderlich S, Merkert S, Hess C, Zweigerdt R, Gruh I, Meyer J, Wagner S, Maier LS, Han DW, Glage S, Miller K, Fischer P, Scholer HR, Martin U. Generation of Induced Pluripotent Stem Cells from Human Cord Blood. Cell Stem Cell. 2009;5(4):434-41.

Gruh I, Martin U. Transdifferentiation of Stem Cells: A Critical View. Adv Biochem Eng Biotechnol. 2009;114:73-106.

Gruh, U. Martin. Transdifferentiation of Stem Cells: A Critical View. Engineering of Stem Cells, U. Martin (editor), Springer-Verlag, 2009, ISBN 978-3-540-88805-5.

2008

Wunderlich S, Gruh I, Winkler ME, Beier J, Radtke K, Schmiedl A, Groos S, Haverich A, Martin U. Type Ii Pneumocyte-Restricted Green Fluorescent Protein Expression after Lentiviral Transduction of Lung Epithelial Cells. Hum Gene Ther. 2008;19(1):39-52.

Winkler ME, Mauritz C, Groos S, Kispert A, Menke S, Hoffmann A, Gruh I, Schwanke K, Haverich A, Martin U. Serum-Free Differentiation of Murine Embryonic Stem Cells into Alveolar Type Ii Epithelial Cells. Cloning Stem Cells. 2008;10(1):49-64.

Gruh I, Wunderlich S, Winkler M, Schwanke K, Heinke J, Blomer U, Ruhparwar A, Rohde B, Li RK, Haverich A, Martin U. Human Cmv Immediate-Early Enhancer: A Useful Tool to Enhance Cell-Type-Specific Expression from Lentiviral Vectors. J Gene Med. 2008;10(1):21-32.

2007

Ruhparwar A, Er F, Martin U, Radke K, Gruh I, Niehaus M, Karck M, Haverich A, Hoppe UC. Enrichment of Cardiac Pacemaker-Like Cells: Neuregulin-1 and Cyclic Amp Increase I(F)-Current Density and Connexin 40 Mrna Levels in Fetal Cardiomyocytes. Med Biol Eng Comput. 2007;45(2):221-7.

2006

Gruh I, Beilner J, Blomer U, Schmiedl A, Schmidt-Richter I, Kruse ML, Haverich A, Martin U. No Evidence of Transdifferentiation of Human Endothelial Progenitor Cells into Cardiomyocytes after Coculture with Neonatal Rat Cardiomyocytes. Circulation. 2006;113(10):1326-34.

2005

Gruh I, Schwanke K, Wunderlich S, Blomer U, Scherr M, Ganser A, Haverich A, Martin U. Shuttle System Allowing Simplified Cloning of Expression Cassettes into Advanced Generation Lentiviral Vectors. Biotechniques. 2005;38(4):530, 2, 4.

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