Adult bone marrow-derived cells do not acquire functional attributes of cardiomyocytes when transplanted into peri-infarct myocardium.
The cardiomyogenic potential of adult bone marrow (BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca(2+)](i)) transients in response to membrane depolarization in situ. Low-density mononuclear (LDM) BM cells, c-kit-enriched (c-kit(enr)) BM cells, and highly enriched lin(-) c-kit(+) BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9-10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy (TPLSM) to monitor action potential-induced [Ca(2+)](i) transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca(2+)](i) transients were found to occur synchronously in host cardiomyocytes along the graft-host border and in areas remote from the infarct, they were absent in all of the >3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart.
Scherschel
John A
JA
Department of Pediatrics, Division of Cardiology, Wells Center for Pediatric Research, Indianapolis, Indiana 46202, USA.
Soonpaa
Mark H
MH
Srour
Edward F
EF
Field
Loren J
LJ
Rubart
Michael
M
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D019070:Cell Lineage; D017690:Cell Transplantation; D002645:Chickens; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology*
D018952:Antigens, CD34; D049452:Green Fluorescent Proteins; D002118:Calcium