Endocrine Pharmacology

Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells

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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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Author information

Correspondence to Zhong-chao Han.

Additional information

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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Keywords

  • prevention
  • diabetic angiopathis
  • transplantation
  • endothelial cells
  • stem cells

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