ABSTRACT
Acute myocardial infarction (AMI) is the most critical heart disease. Mesenchymal stem cells (MSCs) have been widely used as a therapy for AMI for several years. The human placenta has emerged as a valuable source of transplantable cells of mesenchymal origin that can be used for multiple cytotherapeutic purposes. However, the different abilities of first trimester placental chorion mesenchymal stem cells (FCMSCs) and third trimester placental chorion mesenchymal stem cells (TCMSCs) have not yet been explored. In this study, we aimed to compare the effectiveness of FCMSCs and TCMSCs on the treatment of AMI. FCMSCs and TCMSCs were isolated and characterized, and then they were subjected to in vitro endothelial cell (EC) differentiation induction and tube formation to evaluate angiogenic ability. Moreover, the in vivo effects of FCMSCs and TCMSCs on cardiac improvement were also evaluated in a rat MI model. Both FCSMCs and TCMSCs expressed a series of MSCs surface markers. After differentiation induction, FCMSCs-derived EC (FCMSCs-EC) exhibited morphology that was more similar to that of ECs and had higher CD31 and vWF levels than TCMSCs-EC. Furthermore, tube formation could be achieved by FCMSCs-EC that was significantly better than that of TCMSCs-EC. Especially, FCMSCs-EC expressed higher levels of pro-angiogenesis genes, PDGFD, VEGFA, and TNC, and lower levels of anti-angiogenesis genes, SPRY1 and ANGPTL1. In addition, cardiac improvement, indicated by left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF), could be observed following treatment with FCMSCs, and it was superior to that of TCMSCs and Bone marrow MSCs (BMSCs). FCMSCs exhibited a superior ability to generate EC differentiation, as evidenced by in vitro morphology, angiogenic potential and in vivo cardiac function improvement; further, increased levels of expression of pro-angiogenesis genes may be the mechanism by which this effect occurred.
ABSTRACT
In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and exosomes may play a major role. Here, we acquired a special kind of MSCs from the bone marrow of surgically resected tissue from the hand of a patient with polydactyly. Experiments were focused on the role of polydactyly bone marrow-derived MSCs (pBMSCs) in osteoarthritis. The results showed that the pBMSCs had a greater ability than the BMSCs to differentiate into chondrocytes. Mechanistically, the expression of BMP4 was significantly higher in the pBMSCs than it was in the BMSCs. Furthermore, we showed that the migration and proliferation of chondrocytes were stimulated by exosomes secreted by pBMSC (pBMSC-EXOs). Notably, the downregulation of BMP4 in pBMSCs by siRNA inhibited both the chondrogenic differentiation potential of the MSCs and the function of the chondrocytes. In addition, the injection of pBMSC-EXOs and BMSC-EXOs attenuated OA in an OA mouse model, but the pBMSC-EXOs had a superior therapeutic effect compared with that of the BMSC-EXOs. Taken together, the data indicate that pBMSCs have greater ability to differentiate into chondrocytes and regulate chondrocyte formation through BMP4 signaling. Therefore, pBMSC-EXOs may represent a novel treatment for OA.
ABSTRACT
Human embryonic germ cells (hEGCs) are stem cells cultured from primordial germ cells, which reside in human embryonic genital ridges in vivo. In this study, hEGCs were induced to differentiate into cardiomyocytes by treatment with ascorbic acid in vitro and the effects of hEGC transplantation on rat models of acute myocardial infarction (AMI) were investigated. hEGCs were incubated with differentiation medium containing ascorbic acid at various concentrations. Levels of GATA-4 expression were measured to identify the optimal concentration of the inductor. Immunofluorescence microscopy was used to detect the expression of Cx43 on the induced cells. The hEGCs were injected into the myocardium of rats with AMI. The expression levels of MAB1281 and GATA-4 were used to indicate the survival, migration, distribution and differentiation of transplanted cells. The results revealed the positive expression of GATA-4, Cx43 and cardiac troponin T (cTnT) in differentiated cells, and immunocytochemistry showed that transplanted cells highly expressed GATA-4 and MAB1281. hEGCs were successfully induced to differentiate into cardiomyocytes by ascorbic acid in optimal concentrations in vitro and the transplanted hEGCs survived and differentiated into cardiomyocytes.