The Influence Of Diabetic Microenvironment On The Proliferation, Apoptosis, Differentiation And Transplantation Of Adipose-derived Stem Cells

Objective : From the viewpoint of the changing of diabetic microenvironment,we studied the influence of advanced glycation end products(AGEs)and high glucose environment on the proliferation,apoptosis and differentiation of human adipose-derived stem cells(hASCs).Moreover,we studied the effect of rat adipose-derived stem cells(rASCs)and rat adipose-harvested nucleated cells(rANCs)transplantation on the rats’ diabetic wound.Methods:We studied the changing of proliferation,apoptosis and stem cell specific antigen presentation of hASCs under the co-cultivation system contained AGEs and high glucose.We harvested and cultivated the rASCs derived from normal and diabetic rat and used those cells back to the wounds of normal or diabetic rat each.The healing rate and histological changing will be recorded and compared.Results : AGEs and high glucose co-cultivation will inhibited the proliferation and lead to apoptosis in the late stage,the endothelial cell directed differentiation will also be inhibited,however,the presentation of CD34 will be increased which presented on the early endothelial cells.The result of cell factor array indicated AGEs and high glucose environment up-regulated GRO、MCP-1 and down regulated u-PAR that will inhibit the proliferation and transference of endothelial cell.The harvest of rANCs will raise the presentation of specific antigen on ASCs,and after cultivation the ASCs antigen presented cell population will be more.The diabetic rat rASCs(d-rASCs)grows less,bigger,older,low activated,more pseudopodia than normal rASCs.rASCs will promote the healing of diabetic or normal wound thus d-rASCs can only promote wound healing under normal microenvironment.The healing effect of d-rASCs transplantation will be more excessive than rANCs transplantation in the late stage of normal wound.The rASCs transplantation induced more adipose tissue regeneration in the early stage and more granulation filling,more epithelium regeneration in the late stage.The connection between granulation and the edge of wound is tighter after rASCs transplantation.Conclusion:hASCs will be influenced under AGEs and high glucose environment on the proliferation,apoptosis and stabilization.The endothelial cell directed differentiation and maturation is inhibited under AGEs and high glucose environment.The changing of cell factors in the intervened hASCs inhibited the proliferation and transference of endothelial cell.The proliferation of d-rASCs is lower than normal rASCs,and less effective than normal rASCs in wound healing,but more effective than rANCs transplantation and blank control.The AGEs and high glucose cooperated and rivalry effects on hASCs built the microenvironment basis of non-healing wound in the diabetic skin.