HIF-1? Gene-modified Stem Cell Adhered Collagen Scaffold Promotes Nerve Repair After Traumatic Brain Injury

Objective:We construct a model of Traumatic brain injury(TBI)in SD rats by using the modified free-falling Feeney method to investigate the effects of transplantation of HIF-1? modified Umbilical Mesenchymal Stem Cells(UCMSCs)and Extracellular matrix(ECM)complex on nerve repair after Traumatic brain injury in rats.Methods:HIF-1? gene was transfected into UCMSCs and the expression of HIF-1? gene in UCMSCs was identified by Western Blot.ECM obtained by chemical extraction method was identified by Hematoxylin Eosin(HE)staining,and the retention of collagen was proved by immunohistochemical staining.Select 30 weight in 220-260 g,in the male SD rat model of rat by Feeney moderate TBI,randomly divided into 5 groups(each group 6)A group of brain trauma saline area transplantation,transplantation UCMSCs brain trauma group B area,brain trauma group C area transplantation of ECM,group D brain trauma area transplant HIF-1? gene-modified UCMSCs,brain trauma area transplantation group E HIF-1? gene-modified UCMSCs and decellularized scaffolds complex,postoperative 1 day for transplantation,Improved Neurological deficits(mNSS,Modified Neurological Severity Scores)were evaluated in rats of different experimental groups 1 day,7 days,14 days,and 28 days after brain trauma,respectively,and the expression of CREB(CampResponse Element binding protein)gene was identified.Result:UCMSCs were obtained by tissue mass culture,and fibro-like cells were observed in morphology.Immunofluorescence assay showed CD105 positive phenotype,which was consistent with MSCs surface marker.Western Blot confirmed that the expression of HIF-1? was significantly increased in UCMSCs transfected with Lipofectamine2000.The acellular gel scaffold obtained by chemical extraction was obviously removed by HE staining,and the collagen was preserved by immunohistochemistry.At the beginning of 2 weeks after cell transplantation,the behavioral scores of the HIF-1?-UCMSCs group were significantly lower than those of the control group(P<0.05).CREB protein expression in UCMSCs and Extracellular matrix(ECM,Extracellular Matrix)group was significantly higher than that in saline group(P<0.05).CREB protein expression was significantly increased in the HIF-1?-UCMSCs group compared with the UCMSCs group(P<0.05).CREB protein expression in HIF-1?-UCMSCs +ECM group was significantly higher than that in UCMSCs group,ECM group and HIF-1?-UCMSCs group(P<0.05).In conclusion:UCMSCs,ECM and HIF-1?-UCMSCs of rats with moderate TBI injury can repair nerve injury after TBI to different degrees.The combination of UCMSCs,HIF-1?,and ECM was more effective than monotherapy.