Transplantation of bone marrow stromal cells overexpressing human vascular endothelial growth factor 165 enhances tissue repair in a rat model of radiation-induced injury

摘要

Background The multilineage differentiation potential ability of bone marrow stromal cells (BMSCs) showed great potential in tissue engineering,while vascular endothelial growth factor 165 (VEGF165) promotes vasculogenesis and further promotes tissue regeneration.This study aimed to assess the ability of rat BMSCs expressing human VEGFA165 (hVEGF165) to promote tissue repair in rat model of radiation-induced injury.Methods Rat BMSCs were isolated from the tibia.Plasmid DNA expressing hVEGF165 was stably transfected into BMSCs using liposomes.The right hindlimb muscle of 40 rats was irradiated using a 60Co y source (total dose 30 Gy).The animals were divided into four groups (n=10):not injected with BMSCs (control; group 1) or intramuscularly injected two times (once in 2 weeks) with pcDNATM3.1-transfected BMSCs (group 2),untransfected BMSCs (group 3),or hVEGF165-transfected BMSCs (group 4).Angiography was performed 1 week after the last injection of BMSCs; samples of the hindlimb muscle were subjected to transmission electron microscopy,ultrastructural analysis,reverse transcription-PCR (RT-PCR),Western blotting,and immunohistochemistry.Results Rat BMSCs with multipotent differentiation capacity were isolated,hVEGF165-transfected BMSCs overexpressed hVEGF165 mRNA and protein.Injection of BMSCs (groups 2-4) increased the average vessel number,density,diameter,and cross-sectional area; mRNA expression of the myogenic markers including myoblast determination protein,myogenin,and α-smooth muscle actin; and CD31 protein expression; and promoted the repair of blood vessels and myofibers after radiation-induced injury compared to group 1; each of these parameters and hVEGF165 mRNA or protein expression were markedly improved in rats injected with hVEGF165-transfected BMSCs compared to groups 2 and 3.Conclusions BMSCs expressing hVEGF165 enhanced the repair of radiation-induced tissue injury by promoting vasculogenesis and muscle fiber regeneration.BMSCs expressing hVEGF165 may have potential clinical applications.