Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.
The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.
Murry
Charles E
CE
Department of Pathology, Box 357470, Room D-514 HSB, University of Washington, Seattle, Washington 98195, USA. murry@u.washington.edu
Soonpaa
Mark H
MH
Reinecke
Hans
H
Nakajima
Hidehiro
H
Nakajima
Hisako O
HO
Rubart
Michael
M
Pasumarthi
Kishore B S
KB
Virag
Jitka Ismail
JI
Bartelmez
Stephen H
SH
Poppa
Veronica
V
Bradford
Gillian
G
Dowell
Joshua D
JD
Williams
David A
DA
Field
Loren J
LJ
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D012038:Regeneration; D019076:Transgenes / Q000235:genetics