Cardiomyoblast-like Cells Differentiated from Human Adipose Tissue-Derived Mesenchymal Stem Cells Improve Left Ventricular Dysfunction and Survival in a Rat Myocardial Infarction Model

Abstract

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.

Application of the cell sheet technique in tissue engineering

“…The MSC sheet reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Okura et al (31) induced human ADMSCs (hADMSCs) to differentiate into cardiomyoblast-like cells (CLCs) with dimethylsulfoxide, which were used to treat myocardial infarction in a nude rat model. The beneficial effects on cardiac function of hADMSC sheets and CLCs sheets were compared.…”

Once fat was fat and that was that : our changing perspectives on adipose tissue

“…96 This process has also been observed in human ADSCs cultured in the presence of dimethylsulfoxide. 124 Furthermore, such cells were used to improve cardiac function and increase survival rate in a rodent model of myocardial infarction. 124 Similar results were obtained in experiments in which undifferentiated ADSCs were transplanted into rodent 125,126 and porcine 127 infarcted hearts.…”

“…124 Furthermore, such cells were used to improve cardiac function and increase survival rate in a rodent model of myocardial infarction. 124 Similar results were obtained in experiments in which undifferentiated ADSCs were transplanted into rodent 125,126 and porcine 127 infarcted hearts. These data suggest that at least in non-human models of myocardial infarction, ADSCs may be used to repair damaged cardiac tissue, although their utility in humans is still not known and requires further investigation.…”

Human Cardiac Progenitor Cell Grafts as Unrestricted Source of Supernumerary Cardiac Cells in Healthy Murine Hearts

“…Nevertheless, recent evidences suggest that adult progenitor cells can be used to fabricate ex vivo engineered cardiac tissue to be implanted in the injured myocardium. To this aim, progenitor cells can be appropriately grown on polymeric scaffolds [2,3] or, alternatively, thermo-responsive surfaces [4][5][6]. Following the latter procedure, scaffoldless tissue sheets fabricated using clonally expanded stem cell antigen-1 positive (Sca-1 pos ) progenitor cells (CPCs) isolated from murine hearts, prevascularized [7] and transplanted into hearts with experimental myocardial infarction have shown to prevent cardiac Author contributions: G.F. and S.P.…”