Cyclosporin A Reduced Mesenchymal Stem Cells Apoptosis From Hypoxia-reoxygenation

Bone marrow contains a population of progenitor cells known as mesenchymal stem cells (MSCs), which have the capability to colonize different tissues, replicate, and differentiate into multilineage cells. Because of their advantages, such as ease of obtaining by a simple routine bone marrow aspiration, ability to self-renew and pluri-potential of differentiation, MSCs have been considered as one of the most promising candidates of autologous cells for both cell therapy and gene therapy of mesenchymal tissues.Although mesenchymal stem cells (MSCs) are being tested clinically for cardiac repair, the majority of transplanted cells undergo apoptosis in the ischemic heart because of the effects of hypoxia-reoxygenation, poor blood supply, and other proapoptotic factors. Several experimental and clinical studies suggest that cyclosporin A (CSA) treatment reduces apoptosis in some cell lines. However, CSA effect on the apoptosis of MSCs is still unclear, we investigated whether CSA inhibits hypoxia-reoxygenation -induced apoptosis in MSCs. Our data showed incubation with 0.5-5 μmol/L CSA dose dependently decreased hypoxia-reoxygenation -induced apoptosis. CSA inhibited the hypoxia-reoxygenation -induced CSA inhibited the hypoxia-reoxygenation-induced release of cytochrome C, translocation of AIF,and restore mitochondrial potential. We proposed that incubation MSCs with CSA before transplantation would improve MSCs viability and thereby potentially improve MSCs therapy for heart disease.OBJECTIVES: The goal of this study was to pretreatment mesenchymal stem cellswith cyclosporin A reduce the apoptosis of MSCs in hypoxia -reoxygenation insult.METHODS: Mesenchymal stem cells from bone marrow were pretreated by CSA. Cell apoptosis was assayed in vitro after hypoxia-reoxygenation treatment. Loss in mitochondrial transmembrane potential (ΔΨm), release of cytochrome C, translocation of AIF and activation of caspase -3 were tested.RESULTS:Incubation with 0.5-5 μmol/L CSA dose dependently decreased hypoxia-reoxygenation-induced apoptosis, CSA inhibited the hypoxia-reoxygenation-induced release of cytochrome C, translocation of AIF, activation of caspase -3 and restore mitochondrial potential.CONCLUSIONS: Cyclosporin a (CSA) is effective in preventing hypoxia-reoxygenation-induced apoptosis in MSCs.We proposed that incubation MSCs with CSA before transplantation would improve MSCs viability and thereby potentially improve MSC therapy for heart disease.