Effect Of TGF-?1 Expression On Early Immune Inflammatory Response In Peripheral Nerve Xenotransplantation Mice After HAMSCs Therapy

BACKGROUND:Peripheral nerve defects are clinically common diseases,peripheral nerve xenotransplantation is one of the surgical treatment methods.However,the major obstacle in peripheral nerve xenotransplantation is acute immune rejection.hAMSCs transplantation has achieved good curative effect in the treatment of corneal repair and spinal cord injury.hAMSCs that can modulate immune inflammation may be a potential method for treating peripheral nerve xenotransplantation.At the same time,hAMSCs can express TGF-?1,and TGF-?1 is an important immunoregulators,which play an irreplaceable role in early immune inflammatory response.It may be the key molecule for hAMSCs to regulate immune inflammation.In order to intervene in aute immune rejection,we investigated the therapeutic potential of human amniotic mesenchymal stem cells(hAMSCs)and the role of TGF-?1 which involves regulatory T and B cells in immune tolerance following peripheral nerve xenotransplantation.OBJECT:To investigate the therapeutic potential of human amniotic mesenchymal stem cells(hAMSCs)and the role of TGF-?1 in immune tolerance following peripheral nerve xenotransplantation,and to provide a theoretical basis for clinical treatment of peripheral nerve defects.METHODS:Sprague-Dawley rat sciatic nerve was transplanted into adult male C57BL/6 mice.In the first experiment,mice were transplanted with hAMSCs(experimental group)or treated with phosphate-buffered saline(PBS;control group).Motor function was evaluated by CatWalk-assisted gait analysis on days 7,14,and 28.In the second experiment,mice were transplanted with hAMSCs expressing a high or low level of TGF-?1(experimental group)or hAMSCs with normal TGF-?1 expression(control group).Sciatic nerve function index(SFI),number of Tregs and Bregs,and interleukin(IL)-10 and TGF-?1 levels were assessed on day 14 after transplantation.The correlation between degree of motor function recovery and immune tolerance was also evaluated.RESULTS:1.Compared with the PBS-treated group,hAMSC transplantation improved the SFI of xenografted mice.2.Compared with the low-and normal-expressing TGF-?1 of hAMSCs treatment group,the high expressing TGF-?1 of hAMSCs treatment can further improved the SFI of xenografted mice,increased the numbers of Treg cells and Breg cells and increased the levels of TGF-?1 and IL-10 in serum.3.The numbers of Tregs,TGF-?-producing Bregs,IL-10-producing Bregs,and serum levels of TGF-?1 and IL-10 were positively correlated with SFI in the 14th day after treatment with hAMSCs.CONCLUSION:1.hAMSCs transplantation by tail vein can improved the SFI of xenografted mice,which may become a potential treatment strategy.2.hAMSCs transplantation can prevent immune rejection and promote functional recovery following peripheral nerve xenotransplantation through TGF-?1 mediated Treg,Breg,TGF-? and IL-10.3.In nerve xenotransplantation mice,TGF-?1 in hAMSCs may be a key regulator of Treg cells and Breg cells to exert immune tolerance.