Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Kaomei Guan - , Institut für Pharmakologie und Toxikologie, Universitätsmedizin Göttingen, Georg-August-Universität Göttingen (Autor:in)
  • Stefan Wagner - , Georg-August-Universität Göttingen (Autor:in)
  • Bernhard Unsöld - , Georg-August-Universität Göttingen (Autor:in)
  • Lars S. Maier - , Georg-August-Universität Göttingen (Autor:in)
  • Diana Kaiser - , Georg-August-Universität Göttingen (Autor:in)
  • Bernhard Hemmerlein - , Georg-August-Universität Göttingen (Autor:in)
  • Karim Nayernia - , Georg-August-Universität Göttingen (Autor:in)
  • Wolfgang Engel - , Georg-August-Universität Göttingen (Autor:in)
  • Gerd Hasenfuss - , Georg-August-Universität Göttingen (Autor:in)

Abstract

Stem cell-based therapy is a promising approach for the treatment of heart failure. Adult stem cells with the pluripotency of embryonic stem cells (ESCs) would be an ideal cell source. Recently, we reported the successful establishment of multipotent adult germline stem cells (maGSCs) from mouse testis. These cultured maGSCs show phenotypic characteristics similar to ESCs and can spontaneously differentiate into cells from all 3 germ layers. In the present study, we used the hanging drop method to differentiate maGSCs into cardiomyocytes and analyzed their functional properties. Differentiation efficiency of beating cardiomyocytes from maGSCs was similar to that from ESCs. The maGSC-derived cardiomyocytes expressed cardiac-specific L-type Ca channels and responded to Ca channel-modulating drugs. Cx43 was expressed at cell-to-cell contacts in cardiac clusters, and fluorescence recovery after photobleaching assay showed the presence of functional gap junctions among cardiomyocytes. Action potential analyses demonstrated the presence of pacemaker-, ventricle-, atrial-, and Purkinje-like cardiomyocytes. Stimulation with isoproterenol resulted in a significant increase in beating frequency, whereas the addition of cadmium chloride abolished spontaneous electrical activity. Confocal microscopy analysis of intracellular Ca in maGSC-derived cardiomyocytes showed that calcium increased periodically throughout the cell in a homogenous fashion, pointing to a fine regulated Ca release from intracellular Ca stores. By using line-scan mode, we found rhythmic Ca transients. Furthermore, we transplanted maGSCs into normal hearts of mice and found that maGSCs were able to proliferate and differentiate. No tumor formation was found up to 1 month after cell transplantation. Taken together, we believe that maGSCs provide a new source of distinct types of cardiomyocytes for basic research and potential therapeutic application.

Details

OriginalspracheEnglisch
Seiten (von - bis)1615-1625
Seitenumfang11
FachzeitschriftCirculation research
Jahrgang100
Ausgabenummer11
PublikationsstatusVeröffentlicht - Juni 2007
Peer-Review-StatusJa

Externe IDs

PubMed 17478732

Schlagworte

Schlagwörter

  • Cardiac differentiation, Cell transplantation, Gap junction, L-type Ca channels, Spermatogonial stem cells