Dr. sc. nat. Christian Zuppinger
Klinik und Poliklinik für Kardiologie
DKF/Kardiologie, MEM E808
University of Bern
Phone: +41 31 632 91 43
Activties and Research Interests
Cardiomyocytes are terminally differentiated muscle cells in the adult organism and regeneration is limited. This is a worrisome fact, since ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function.
As in vitro model, isolated organs and primary cells from rodents have been the standard in research and toxicology so far, but there is a need for better models. Therefore, we are developing a model comprising both the advantages of scaffold-free 3D cell culture and cardiomyocytes derived from induced pluripotent stem cells (iPSC) of human origin. Myocardial microtissues (MT) were generated by self-assembly in multi-well hanging drop cultures. Prior to the use of the iPSC-derived cells, cardiomyocytes were characterized after 10 days in 2D standard culture and showed highly differentiated myofibrils positive for sarcomeric proteins such as myomesin, myosin, cardiac actin and desmin. The cells showed spontaneous contractile activity and connexin-43 positive gap junctions. In the hanging drop cultures, iPSC-derived cardiomyocytes formed MT’s within 4 days, contracting up to 3 weeks recorded by optical motion tracking. Morphological and functional characterization underline that this model might become a valuable tool for substance safety testing in the future.
Dimitrakits P, Romay-Ogando MI, Suter TM, Zuppinger C. Effects of doxorubicin cancer therapy on autophagy and the ubiquitin-proteasome system in long-term cultured adult rat cardiomyocytes. Cell Tissue Res 2012; 350(2):361-72
Chiusa M, Hool SL, Truetsch P, Djafarzadeh S, Jakob SM, Seifriz F, Scherer SJ, Suter TM, Zuppinger C (corresponding author), Zbinden S. Cancer therapy modulates VEGF signaling and viability in adult rat cardiac microvascular endothelial cells and cardiomyocytes. J Mol Cell Cardiol 2012; 52:1162-1175
Zuppinger C, Suter, T.M. Cancer Therapy-Associated Cardiotoxicity and Signaling in the Myocardium. J Cardiovasc Pharmacol. 2010, Apr. 9.
Pentassuglia L, Graf M, Lane HA, Kuramochi Y, Cote GM, Timolati F, Sawyer DB, Zuppinger C. and Suter TM. Inhibition of ErbB2 by receptor tyrosine kinase inhibitors causes myofibrillar structural damage without cell death in adult rat cardiomyocytes. Exp Cell Res 2009; 315:1302-1312
Timolati F, Ott D, Pentassuglia L, Giraud MN, Perriard JC, Suter TM, Zuppinger C. Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation-contraction coupling and reduces oxidative stress in adult rat cardiomyocytes. J Mol Cell Cardiol 2006; 41:845-854
Sawyer DB, Zuppinger C, Miller TA, Eppenberger HM, Suter TM. Modulation of Anthracycline-Induced Myofibrillar Disarray in Rat Ventricular Myocytes by Neuregulin‑1 beta and Anti-erbB2: Potential Mechanism for Trastuzumab-Induced Cardiotoxicity. Circulation. 2002;105:1551-1554