Bone marrow-derived human mesenchymal stem cells express cardiomyogenic proteins but do not exhibit functional cardiomyogenic differentiation potential.
Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC-mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1(+) mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration.
Institute of Clinical and Experimental Transfusion Medicine (IKET), University Hospital Tübingen, Tübingen, Germany.
Georg
G
Siegel
Petra
P
Krause
Stefanie
S
Wöhrle
Patrick
P
Nowak
Miriam
M
Ayturan
Torsten
T
Kluba
Bernhard R
BR
Brehm
Birgid
B
Neumeister
David
D
Köhler
Peter
P
Rosenberger
Lothar
L
Just
Hinnak
H
Northoff
Richard
R
Schäfer
D000199:Actins / Q000378:metabolism; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D018920:Coculture Techniques / Q000379:methods; D003470:Culture Media / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D015703:Antigens, CD; D003470:Culture Media; D018994:Myosin Light Chains; D012333:RNA, Messenger; D019210:Troponin I