To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral microangiopathy in diabetic nude mice.
Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immuno-histopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells(EPC).
Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells.
These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.
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Project supported by grants of 863 (No 2003AA205060), National Major Grants for Basic Research (No 001CB5101) from the Ministry of Science and Technology of China.
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