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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Cardiovascular progenitors derived from induced pluripotent stem cells (iPS) improve heart function after myocardial infarction

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  • Andreas Martens - Medizinische Hochschule Hannover, HTTG-Chirurgie, OE6210, Hannover
  • Christina Mauritz - Medizinische Hochschule Hannover, Leibniz Forschungslaboratorien für Biotechnologie und künstliche Organe (LEBAO), OE 6217, Hannover
  • Sebastian Rojas - Medizinische Hochschule Hannover, HTTG-Chirurgie, OE6210, Hannover
  • Tilman Schnick - Medizinische Hochschule Hannover, Leibniz Forschungslaboratorien für Biotechnologie und künstliche Organe (LEBAO), OE 6217, Hannover
  • Robert Zweigerdt - Medizinische Hochschule Hannover, Leibniz Forschungslaboratorien für Biotechnologie und künstliche Organe (LEBAO), OE 6217, Hannover
  • Axel Haverich - Medizinische Hochschule Hannover, HTTG-Chirurgie, OE6210, Hannover
  • Ulrich Martin - Medizinische Hochschule Hannover, Leibniz Forschungslaboratorien für Biotechnologie und künstliche Organe (LEBAO), OE 6217, Hannover
  • Ingo Kutschka - Medizinische Hochschule Hannover, HTTG-Chirurgie, OE6210, Hannover

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch555

doi: 10.3205/11dgch555, urn:nbn:de:0183-11dgch5550

Published: May 20, 2011

© 2011 Martens et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: Induced pluripotent stem (iPS) cells are obtained from somatic cells by reprogramming the genome to a pluripotent state. Cardiovascular progenitor cells derived from iPS cells might be useful for autologous cellular cardiomyoplasty. Flk1 has been described as an early mesodermal and precardiac cell surface marker. The aim of the present study was to evaluate the potential of murine iPS cell derived Flk1+ progenitor cells to give rise to cardiovascular cell types in vitro and in vivo and to improve cardiac function following myocardial infarction in mice.

Materials and methods: Flk1+ progenitor cells were FACS-sorted from differentiating murine iPS cells. They were further cultivated for in vitro characterization or injected into the ischemic myocardium of LAD-ligated mice. Infarcted animals were treated with placebo (PBS, Group A, n=10) or Flk1+ progenitor cells (Group B, N=11, 5x10^5 cells). They underwent conductance catheter (CC) and MRI evaluation two weeks postoperatively to determine functional cardiac outcome. In vivo differentiation was evaluated by immunhistochemistry.

Results: Murine iPS cell-derived Flk1+ progenitor cells gave rise to cardiac troponin T expressing cardiomyocytes, α-smooth muscle actin positive cells and CD31 expressing endothelial cells in vitro and in vivo. Treatment with Flk1+ iPS progenitor cells resulted in a favorable myocardial remodeling as evaluated by CC analysis and MRI: Compared to controls cell treated animals showed a significantly decreased cardiac volume load (enddiastolic volume [EDV]: 27±3µl vs. 19±2µl, p<0.05) and an improved left ventricular function (left ventricular ejection fraction [LV-EF]: 16±1% vs. 31±3%, p<0.01).

Conclusion: iPS cell-derived Flk1+ progenitor cells differentiate into cells of cardiovascular lineages in vitro and in vivo and improve cardiac function after acute myocardial infarction. They are a promising autologous cell source for myocardial restoration in ischemic heart failure.