Effect And Function Of SETD7 In Replicative Senescence Of HAD-MSCs

Mesenchymal stem cells(MSCs)are one of the most widely used adult stem cells in the application of regenerative medicine because of their convenience in obtaining materials and the ability to treat various diseases through autologous and allogeneic transplantation.Due to the limited number of MSCs in vivo,it is necessary to obtain sufficient cells through in vitro expansion and culture before transplantation.However,with the increase in the number of MSCs cultured in vitro,the proliferation and differentiation ability of MSCs decreased significantly and accompanied by the appearance of aging characteristics,resulting in a decline in the quantity and quality of MSCs,which seriously affected the therapeutic effect of transplantation.Therefore,replicative aging of MSCs has become a bottleneck restricting its clinical application.This paper aims at the aging problem of MSCs expansion in vitro,using human Adipose derived mesenchymal stem cells(h AD-MSCs)as a model,aiming to reveal the new mechanism and intervention methods of MSCs replicative senescence.In this thesis,the differential expression genes of MSCs in vitro were screened by analyzing the data of GEO chip.It was found that the expression level of histone methyltransferase SETD7 was significantly increased during the aging process of MSCs.Then using SETD7 as the main research object,the expression change of SETD7 during the passage of MSCs was verified by continuous subculture in vitro.Further inhibiting its activity through small molecules,it was found that the aging process of MSCs is slowed down,and it can maintain its cell proliferation and differentiation ability to a certain extent.Finally,taking its tendon differentiation ability as an example,in the rat model of in situ patellar tendon defect in vivo,it was verified that inhibition of SETD7 activity in MSCs cells can effectively maintain its differentiation ability of tendon system(tendon-related genes and protein expression,extracellular matrix secretion)and can promote tendon regeneration and repair.The findings of this study provide a new molecular mechanism for explaining the aging problems of MSCs cultured in vitro,and provide a potential target for delaying cell aging.