Abstract
Aim:
To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral microangiopathy in diabetic nude mice.
Methods:
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).
Results:
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.
Conclusion:
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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Zhou, B., Cao, Xc., Fang, Zh. et al. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells . Acta Pharmacol Sin 28, 89–97 (2007). https://doi.org/10.1111/j.1745-7254.2007.00476.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00476.x
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