The therapeutic effect of monocyte chemoattractant protein-1 delivered by an electrospun scaffold for hyperglycemia and nephrotic disorders

Int J Nanomedicine. 2014 Feb 17:9:985-93. doi: 10.2147/IJN.S55812. eCollection 2014.

Abstract

Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1), locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77 ± 32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%± 7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%± 5.29% and 43.49%± 9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients.

Keywords: MCP-1; diabetes; electrospinning; islet transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Chemokine CCL2 / administration & dosage*
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / pharmacokinetics
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / therapy
  • Drug Delivery Systems*
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / therapy
  • Islets of Langerhans Transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nanomedicine
  • Tissue Engineering
  • Tissue Scaffolds / chemistry

Substances

  • Blood Glucose
  • Ccl2 protein, mouse
  • Chemokine CCL2