Center for Molecular Medicine Cologne

Pfannkuche, Kurt P - assoc. RG 17

Cardiac tissue engineering


Our lab focusses on induced pluripotent stem cell derived cardiomyocytes. We aim to optimize transplantation of micro-tissues into the myocardium after myocardial infarction. Micro-tissues refer to aggregates of organotypic cells with defined size and cellular composition. Major obstacles to be solved include the occurrence of cardiac arrhythmia after cell transplantation into the diseased myocardium, the low efficiency of cardiomyocyte engraftment and the technological deficits in cell preparation. Current projects of the group address questions of intramyocardial cell engraftment; improved bioreactor technologies and 3D culture models are being developed. Recently, we have made substantial progress in the generation of cardiac organoids from human induced pluripotent stem cells and expand our activity in the field of organoids research. Together with our partner laboratory at the Department for Physical Chemistry (Prof. Dr. Annette Schmidt) we investigate novel biomaterials for cell and organoid culture as well for bioreactor-based stem cell culture.

Today it remains unclear which strategies will result in a stem cell-based therapy of cardiac diseases in the future and we follow additional strategies beside direct cell transplantation. We are interested in developing artificial cardiac tissues that are generated from pluripotent stem cell derived cells. In this respect, formation of artificial vessel structures to provide oxygen and nutrients to the artificial myocardium is part of ongoing research activities. Finally, we are addressing mechanism of cardiac fibrosis with focus on the role of cardiomyocytes in cardiac matrix homeostasis. In this respect our advanced human cardiac organoids serve as model system for human cardiac physiology and pathophysiology in vitro.

Figure 1

Clinical and Medical Relevance

Cardiovascular diseases are among the major causes of death in the western hemisphere. Stem cell based technologies will pave the way towards novel therapies of cardiac diseases such as cardiac infarction. Our research strategy will generate knowledge in the field of artificial tissues and organs for future therapies in vivo as well as novel test systems for pharmaceuticals in vitro.

  • Hamad S, Derichsweiler D, Papadopoulos S, Nguemo F, Šarić T, Sachinidis A,Brockmeier K, Hescheler J, Boukens BJ, Pfannkuche K. Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations. (2019).Theranostics. 9(24), 7222-7238.
  • Sahito RGA, Sheng X, Maass M, Mikhael N, Hamad S, Heras-Bautista CO,Derichsweiler D, Spitkovsky D, Suhr F, Khalil M, Brockmeier K, Halbach M, Saric T, Hescheler J, Krausgrill B, Pfannkuche K. (2019). In Vitro Grown Micro-Tissues for Cardiac Cell Replacement Therapy in Vivo. Cell Physiol Biochem. 52(6), 1309-1324.
  • Heras-Bautista CO, Mikhael N, Lam J, Shinde V, Katsen-Globa A, Dieluweit S, Molcanyi M, Uvarov V, Jütten P, Sahito RGA, Mederos-Henry F, Piechot A, Brockmeier K, Hescheler J, Sachinidis A, Pfannkuche K. Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts. (2019). Acta Biomater. 89, 180-192.
  • Heras-Bautista CO, Katsen-Globa A, Schloerer NE, Dieluweit S, Abd El Aziz OM, Peinkofer G, Attia WA, Khalil M, Brockmeier K, Hescheler J, Pfannkuche K. The influence of physiological matrix conditions on permanent culture of induced pluripotent stem cell-derived cardiomyocytes. (2014). Biomaterials 35(26), 7374-85.
  • Sheng X, Reppel M, Nguemo F, Mohammad FI, Kuzmenkin A, Hescheler J, Pfannkuche K. Human pluripotent stem cell-derived cardiomyocytes: response to TTX and lidocain reveals strong cell to cell variability. (2012). PLoS One. 7(9):e45963.
  • Hamad S, Derichsweiler D, Gaspar JA, Brockmeier K, Hescheler J, Sachinidis A, and Pfannkuche KP (2022). High-efficient serum-free differentiation of endothelial cells from human iPS cells. Stem Cell Res Ther13, 251. doi:10.1186/s13287-022-02924-x.
  • Hamad S, Derichsweiler D, Hescheler J, and Pfannkuche K (2022). Scalable Generation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Methods Mol Biol2454, 145-161. doi:10.1007/7651_2021_395.
  • Jahn P, Karger RK, Soso Khalaf S, Hamad S, Peinkofer G, Sahito RGA, Pieroth S, Nitsche F, Lu J, Derichsweiler D, Brockmeier K, Hescheler J, A MS, and Pfannkuche K (2022). Engineering of cardiac microtissues by microfluidic cell encapsulation in thermoshrinking non-crosslinked PNIPAAm gels. Biofabrication14. doi:10.1088/1758-5090/ac73b5.
  • Hamad S, Derichsweiler D, Hescheler J, Pfannkuche K. Scalable Generation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Methods Mol Biol. 2021 Oct 19. doi: 10.1007/7651_2021_395. Online ahead of print. PMID: 34664217
  • Daliri K, Pfannkuche K, and Garipcan B (2021). Effects of physicochemical properties of polyacrylamide (PAA) and (polydimethylsiloxane) PDMS on cardiac cell behavior. Soft Matter17, 1156-1172. doi:10.1039/d0sm01986k.
  • Peinkofer G, Maass M, Pfannkuche K, Sachinidis A, Baldus S, Hescheler J, Saric T, and Halbach M (2021). Persistence of intramyocardially transplanted murine induced pluripotent stem cell-derived cardiomyocytes from different developmental stages. Stem Cell Res Ther12, 46. doi:10.1186/s13287-020-02089-5.