Fate of undifferentiated mouse embryonic stem cells within the rat heart: role of myocardial infarction and immune suppression.
Abstract It has recently been suggested that the infarcted rat heart microenvironment could direct pluripotent mouse embryonic stem cells to differentiate into cardiomyocytes through an in situ paracrine action. To investigate whether the heart can function as a cardiogenic niche and confer an immune privilege to embryonic stem cells, we assessed the cardiac differentiation potential of undifferentiated mouse embryonic stem cells (mESC) injected into normal, acutely or chronically infarcted rat hearts. We found that mESC survival depended on immunosuppression both in normal and infarcted hearts. However, upon Cyclosporin A treatment, both normal and infarcted rat hearts failed to induce selective cardiac differentiation of implanted mESC. Instead, teratomas developed in normal and infarcted rat hearts 1 week and 4 weeks (50% and 100%, respectively) after cell injection. Tight control of ESC commitment into a specific cardiac lineage is mandatory to avoid the risk of uncontrolled growth and tumourigenesis following transplantation of highly plastic cells into a diseased myocardium.
He
Qing
Q
Department of Rehabilitation and Geriatrics, Laboratory of Biology of Aging, Geneva University Hospitals, Geneva, Switzerland.
Trindade
Pedro T
PT
Stumm
Michael
M
Li
Jian
J
Zammaretti
Prisca
P
Bettiol
Esther
E
Dubois-Dauphin
Michel
M
Herrmann
François
F
Kalangos
Afksendyios
A
Morel
Denis
D
Jaconi
Marisa E
ME
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D016572:Cyclosporine / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000378:metabolism; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013724:Teratoma / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left
D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine