Lineage Conversion of skeletal muscle derived precursor cells into cardiomyocytes - A promising autologous cell source for cardiac cell therapy

Question: Cardiac cell transplantation is a promising approach for cardiac regeneration in heart failure patients. However, the ideal cell source has not been found yet. In the presented work we induced a lineage conversion of skeletal muscle derived precursors into cardiomyocytes avoiding gene manipulation, which can be easily translated into a clinical application.

Methods: Skeletal precursor cells were isolated from adult C57/BL6 mice. Following a primary expansion and purification according to a skeletal myoblast isolation protocol, the cell product was further cultured under hanging drop culture conditions. The forming cell clusters were characterized by immunohistochemistry and single cell patch-clamping.

Results: Under hanging drop culture conditions the purified cells showed a high lineage conversion rate towards cardiomyocyte-like phenotype. Besides synchronous beating of the clusters, these cells were highly positive for cardiac troponin, connexin43, cardiac myosin heavy-chain. Electrophysiological assessment under 8 Hz stimulation showed cardiomyocyte like shape of the action-potentials.

Conclusions: Despite an ongoing controversial discussion about skeletal precursor cells a cell source for cardiac cell therapy, we confirmed successful lineage conversion of those cells into a cardiomyocyte-like phenotype. This provides an outstanding alternative cell source for cardiac cell therapy which can be easily translated into a clinical application.