External Force Promotes The Migration And Differentiation Of ASCs By Regulation Of Stiffness-dependent Dynamin Expression

Purpose:The biological function of adipose-derived stem/progenitor cells(ASCs)is very important in adipose regeneration.External force could increase adipose tissue stiffness,which promotes the migration but inhibits the differentiation of ASCs.In our previous study,we found the expression of Dynamin(Dyn)was regulated by external force and related to the migration and differentiation of ASCs.Thus,the underlying mechanism of ASCs biological function regulated by the external force is meaningful for adipose regeneration.Methods:ASCs were cultured under different stiffness conditions and the expression of Dyn was observed in vitro.In vivo,Sprague-Dawley rats were randomly divided into four groups.Dyn4a,an inhibitor of Dyn,was used to regulate Dyn in groin adipose tissue under external force(Group 4)and normal groin adipose tissue(Group2).Compared with groin adipose tissue under external force(Group 3)and normal groin adipose tissue(Group 1).The migration of ASCs was observed by immunofluorescence of CD34~+cells.The adipogenesis was observed by expression of PPAR-?.Regeneration was compared by immunofluorescence of perilipin and fibrosis was compared by histological examination and expression of?-SMA.The final volume in all groups were compared.Results:The expression of Dyn in ASCs was promoted by increased stiffness in vitro.In vivo,the number of ASCs(CD34~+cells)was higher in groin adipose tissue under external force than normal(Group 1),but lower in groin adipose tissue using Dyn4a under external force(Group 4)than Group 3 on day 1 and 3.However,the adipogenesis of ASCs,including perilipin level and PPAR-?expression was higher in Group 4 than Group 3,also the fibrosis level and?-SMA expression was lower in Group4 than Group 3 on day 9.The final volume of adipose tissue was higher in Group 1 than other three groups on.Conclusions:The external force increases the stiffness of adipose tissue,which increases the expression of Dyn in ASCs.Dyn can promote ASCs migration but inhibit adipogenesis.Regulation of Dyn expression can promote both the migration and adipogenesis of ASCs,as the long-term adipose tissue regeneration under external force.