Cardiomyoblast-like cells differentiated from human adipose tissue-derived mesenchymal stem cells improve left ventricular dysfunction and survival in a rat myocardial infarction model.
Adipose tissue-derived mesenchymal stem cells (ADMSCs) are multipotent cells. Here we examined whether human ADMSCs (hADMSCs) could differentiate into cardiomyoblast-like cells (CLCs) by induction with dimethylsulfoxide and whether the cells would be utilized to treat cardiac dysfunction. Dimethylsulfoxide induced the expression of various cardiac markers in hADMSCs, such as alpha-cardiac actin, cardiac myosin light chain, and myosin heavy chain; none of which were detected in noncommitted hADMSCs. The induced cells were thus designated as hADMSC-derived CLCs (hCLCs). To confirm their beneficial effect on cardiac function, hCLC patches were transplanted onto the Nude rat myocardial infarction model, and compared with noncommitted hADMSC patch transplants and sham operations. Echocardiography demonstrated significant short-term improvement of cardiac function in both the patch-transplanted groups. However, long-term follow-up showed rescue and maintenance of cardiac function in the hCLC patch-transplanted group only, but not in the noncommitted hADMSC patch-transplanted animals. The hCLCs, but not the hADMSCs, engrafted into the scarred myocardium and differentiated into human cardiac troponin I-positive cells, and thus regarded as cardiomyocytes. Transplantation of the hCLC patches also resulted in recovery of cardiac function and improvement of long-term survival rate. Thus, transplantation of hCLC patches is a potentially effective therapeutic strategy for future cardiac tissue regeneration.
Okura
Hanayuki
H
Department of Somatic Stem Cell Therapy, Foundation for Biomedical Research and Innovation , Kobe, Japan .
Matsuyama
Akifumi
A
Lee
Chun-Man
CM
Saga
Ayami
A
Kakuta-Yamamoto
Aya
A
Nagao
Anna
A
Sougawa
Nagako
N
Sekiya
Naosumi
N
Takekita
Kazuhiro
K
Shudo
Yashuhiro
Y
Miyagawa
Shigeru
S
Komoda
Hiroshi
H
Okano
Teruo
T
Sawa
Yoshiki
Y
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D001483:Base Sequence; D017690:Cell Transplantation; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000628:therapy*
D017931:DNA Primers