Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel.
OBJECTIVE
As the capability of human mesenchymal stem cells (hMSC) to engraft, differentiate and improve myocardial function cannot be studied in humans, exploration was performed in a xenomodel.


METHODS
The rats were divided into three groups depending on the type of rats used (Rowett nude (RNU) or Fischer rats +/- immunosuppression). Different groups were treated with intramyocardial injection of hMSC (1-2 million) either directly or three days after ligation of the left anterior descending artery (LAD). Myocardial function was investigated by echocardiography. The hMSC were identified with fluorescence in situ hybridization and myocardial differentiation was assessed by immunohistochemistry.


RESULTS
When hMSC were injected directly after LAD ligation they could be identified in half (8/16) of the RNU rats (without immunosuppression) at 4 weeks. When injected 3 days after LAD ligation in immunosuppressed RNU rats they were identified in all (6/6) rats at 6 weeks. The surviving hMSC showed signs of differentiation into fibroblasts. No cardiomyocyte differentiation was observed. There was no difference in myocardial function in treated animals compared to controls.


CONCLUSIONS
The hMSC survived in this xenomodel up to 6 weeks. However, hMSC required implantation into immunoincompetent animals as well as immunosuppression to survive, indicating that these cells are otherwise rejected. Furthermore, these cells did not differentiate into cardiomyocytes nor did they improve heart function in this xenomodel.
Grinnemo
Karl-Henrik
KH
Department of Cardiothoracic Surgery and Anaesthesiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Månsson-Broberg
Agneta
A
Leblanc
Katarina
K
Corbascio
Matthias
M
Wärdell
Eva
E
Siddiqui
Anwar J
AJ
Hao
Xiaojin
X
Sylvén
Christer
C
Dellgren
Göran
G
D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007267:Injections; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude