Human umbilical cord blood derived mesenchymal stem cells improve cardiac function in cTnTR141W transgenic mouse of dilated cardiomyopathy

Abstract

Cell transplantation is a promising strategy in regenerative medicine. Beneficial effects of bone marrow mesenchymal stem cells (BM-MSCs) on heart disease have been widely reported. However, the MSCs in these studies have been mainly derived from autologous animals, and data on MSCs from human umbilical cord blood (UCB-MSCs) are still scarce. We investigated whether intramyocardial xenogeneic administration of UCB-MSCs is beneficial for preserving heart function in a cTnTR141W transgenic mouse of dilated cardiomyopathy (DCM). Cultured UCB-MSCs, which were identified by there morphology, differentiation and cell surface markers, were transplanted into cTnTR141W transgenic mice to examine apoptosis, fibrosis, vasculogenesis and the associated Akt pathway. Moreover, we measured the expression levels of VEGF and IGF-1, which are growth factors required for differentiation into cardiomyocytes, and are also involved in cardiac regeneration and improving heart function. One month after transplantation, MSCs significantly decreased chamber dilation and contractile dysfunction in the cTnTR141W mice. MSCs transplanted hearts showed a significant decrease in cardiac apoptosis and its regulation by the Akt pathway. Cardiac fibrosis and cytoplasmic vacuolisation were significantly attenuated in the MSCs group. Importantly, the levels of VEGF and IGF-1 were increased in the MSCs transplanted hearts. In vitro, the MSC-conditioned medium displayed anti-apoptotic activity in h9c2 cardiomyocytes subjected to hypoxia. These results further confirm the paracrine effects of MSCs. In conclusion, UCB-MSCs preserve cardiac function after intramyocardial transplantation in a DCM mouse, and this effect may be associated with reductions in cellular apoptosis, inflammation, hypertrophy and myocardial fibrosis; in addition to; up-regulation of Akt, VEGF and IGF-1; and enhanced angiogenesis.