Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model

Abstract

IntroductionBone marrow mesenchymal stem cells (BMMSCs) have been reported to facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs on liver regeneration after massive hepatectomy is barely studied. Here we explored whether infusion of BMMSCs promotes liver regeneration in a rat massive hepatectomy model.MethodsHypoxia preconditioning was achieved by culturing BMMSCs under a hypoxia environment. Then 85% hepatectomy was performed and hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A group of rats received vascular endothelial growth factor (VEGF) neutralizing antibody perioperatively, and underwent 85% hepatectomy and a subsequent infusion of hypoxia preconditioned BMMSCs to verify the role of VEGF in the effects of BMMSCs on liver regeneration. Liver samples were collected and liver regeneration was evaluated postoperatively.ResultsHypoxia preconditioning enhanced the expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation of hepatocytes, reflected by elevated cyclin D1 expression and proliferating cell nuclear antigen-positive hepatocytes. However, BMMSC infusion did not improve the serum albumin level, liver weight/body weight ratio, and survival after operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated cyclin D1, proliferating cell nuclear antigen-positive hepatocytes, liver weight/body weight ratio, and survival compared with normoxia preconditioned BMMSCs, accompanied by an increased serum albumin level. The level of VEGF in liver homogenate was much higher in hypoxia preconditioned BMMSC-treated animals than in other groups. In addition, the perioperative injection of VEGF neutralizing antibody significantly blocked the therapeutic effects of hypoxia preconditioned BMMSCs on liver injury and regeneration in this model.ConclusionHypoxia preconditioned BMMSCs enhanced liver regeneration after massive hepatectomy in rats, possibly by upregulating the level of VEGF.

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

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Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium

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Carboxymethyl Guar Gum Nanoscaffold as Matrix for Cell Growth In Vitro

“…Studies showed that during inflammatory state, there is metabolic imbalance at the mucosal surface of the tissues causing hypoxia characterized by over expression of hypoxia inducible factor (HIF) [32,33]. The hypoxia preconditioned BM-MSCs have been used for tissue injury in previous studies considering the MSCs which survives the hypoxic stressed condition are adapted to counteract and survive under the conditions prevailing during the injury for its recovery [34]. In our experiment we have checked the effect of hypoxia on cells as well as on scaffolds which was done after treating the cells grown on scaffold with CoCl 2 .…”