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Most of the Dust Has Settled: cKit+ Progenitor Cells Are an Irrelevant Source of Cardiac Myocytes In Vivo.

Resident c-kit+ cells in the heart are not cardiac stem cells

Sultana et al

Nat Comm . 2015;6:8701. doi: 10.1038/ncomms9701.

That cKit+ progenitor cells can transdifferentiate into new cardiac myocytes as a means of regenerating the heart after infarction injury has been hotly debated for nearly 15 years. A recent publication using exhaustive genetic reporters and lineage tracing shows definitively that endogenous cKit+ cells in the heart are in fact endothelial in nature and have an essentially meaningless capacity to make cardiomyocytes in vivo .

The concept that adult stem cells could be used to regenerate the infarction damaged heart to treat heart failure captured the imagination of both the public and scientific community. This concept dates back 14 years with the first description by Orlic et al that cKit+ cells derived from bone marrow could abundantly transdifferentiate into new contracting myocardium when directly injected into the infarcted heart.1 Two years later, Beltrami et al showed that cKit+ progenitors from the heart itself could be extracted, expanded ex vivo, and reinjected into the rodent heart to again abundantly transdifferentiate and create as much as 70% new contracting myocardium.2 Fast forward to the present day and the current picture of myocardial regeneration from cKit+ progenitors or some other adult stem cell population seems rather unlikely. This current picture was made even more concrete with the recent publication of yet another definitive in vivo lineage tracing study for cKit+ cells in the heart by Sultana et al.3

Although cKit+ progenitor cells were originally reported to abundantly regenerate the heart after infarction injury, a number of subsequent papers in the ensuing years from independent groups were unable to repeat these results, despite considerable effort (reviewed in van Berlo and Molkentin).4 The …