The therapeutic role of monocyte chemoattractant protein-1 in a renal tissue engineering strategy for diabetic patients

PLoS One. 2013;8(2):e57635. doi: 10.1371/journal.pone.0057635. Epub 2013 Feb 25.

Abstract

In this study we aim to boost the functional output of the intra-kidney islet transplantation for diabetic patients using a tissue engineered polymeric scaffold. This highly porous electrospun scaffold featured randomly distributed fibers composed of polycaprolactone (PCL) and poliglecaprone (PGC). It successfully sustained murine islets in vitro for up to 4 weeks without detected cytotoxicity. The in vivo study showed that the islet population proliferated by 89% within 12 weeks when they were delivered by the scaffold but only 18% if freely injected. Correspondingly, the islet population delivered by the scaffold unleashed a greater capability to produce insulin that in turn further drove down the blood glucose within 12 weeks after the surgery. Islets delivered by the scaffold most effectively prevented diabetic deterioration of kidney as evidenced by the lack of a kidney or glomerular enlargement and physiological levels of creatinine, urea nitrogen and albumin through week 12 after the surgery. Unlike traditional wisdom in diabetic research, the mechanistic study suggested that monocytes chemoattractant protein-1 (MCP-1) was responsible for the improved preservation of renal functions. This study revealed a therapeutic role of MCP-1 in rescuing kidneys in diabetic patients, which can be integrated into a tissue engineered scaffold to simultaneously preserved renal functions and islet transplantation efficacy. Also, this study affords a simple yet effective solution to improve the clinical output of islet transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Chemokine CCL2 / metabolism*
  • Chemokine CCL2 / pharmacology*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / surgery*
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology
  • Islets of Langerhans Transplantation / methods*
  • Kidney / surgery*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Tissue Engineering / methods*

Substances

  • Blood Glucose
  • CCL2 protein, human
  • Chemokine CCL2
  • Insulin

Grants and funding

The authors acknowledge the financial support from China’s Natural Science Foundation (grant number 30772056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.