Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mono

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lidids
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Aim:To investigate whether the prophylactic local delivery of mobilized periph-eral blood mononuclear cells(M-PBMNC)could prevent peripheral microangio-pathy in diabetic nude mice.Methods:Diabetic nude mice were induced withintraperitoneal injections of streptozotocin.With the time course of diabetes,wedetected the capillary and arteriole density of mice adductor muscles by immuno-histopathy.In situ apoptosis was detected by using TdT-mediated dUTP nickend labeling(TUNEL)methods.M-PBMNC were labeled and locally delivered tothe adductor muscles.Mononuclear cells were also isolated and cultured in vitrofor the detection and counting of endothelial progenitor cells(EPC).Results:Rarefication of capillaries and arterioles,enhanced apoptosis in adductor muscles,and reduced circulating EPC in diabetic nude mice.Prophylactic local delivery ofM-PBMNC halted the progression of microvascular rarefaction in hind-limb skel-etal muscles by inhibiting apoptosis.We detected the survival,migration andincorporation of transplanted M-PBMNC into the murine vasculature in vivo.Inaddition,more EPC were available from M-PBMNC than non-mobilized cells.Conclusion:These results suggested that the prophylactic local delivery ofM-PBMNC may represent a novel approach for the treatment of microvascularcomplications in diabetics. Aim: To investigate whether the prophylactic local delivery of mobilized periph-eral blood mononuclear cells (M-PBMNC) could prevent peripheral microangio-pathy in diabetic nude mice. Methods: Diabetic nude mice were induced with in traititoneal injections of streptozotocin. W the the time course of diabetes, wedetected the capillary and arteriole density of mice adductor muscles by immuno- histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nickend labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered tothe adductor muscles. Mononuclear cells were also isolated and cultured in vitrofor the detection and counting of endothelial progenitor cells (EPC). Results: Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prochylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skel-etal muscles by inhibiting apoptosis. We detected the survival, migration andi ncorporation of transplanted M-PBMNC into the murine vasculature in vivo. addition, more EPC were available from M-PBMNC than non-mobilized cells. Conlusion: These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascularcomplications in diabetics.
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