Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats

Neurosci Lett. 2015 Jun 15:597:84-9. doi: 10.1016/j.neulet.2015.04.038. Epub 2015 Apr 24.

Abstract

Neuropathy is observed in 50% of diabetic patients with diabetic foot. This study attempted to explore the potential role of human mesenchymal stem cells-umbilical cord blood (hMSCs-UC) in femoral nerve (FN) neuropathy. The model rats were established by one time administration of streptozotocin and empyrosis on the dorsal hind foot. At 3d, 7d, 14d after treatment with hMSCs-UC or saline through left femoral artery, the serum NGF was examined by ELISA; NF-200 expression in FN was evaluated by immunohistochemistry; the diameter and roundness of FN, the ratio of capillary and muscular fiber of gastrocnemius were calculated under light microscope; and neuronal degenerations, such as demyelization, axonal atrophy, and loose arrangement of nerve fibers, were observed by electronic microscope. The results showed that, in hMSCs-UC-treated model rats, serum NGF was increased with higher positive rate of NF-200. Although the difference in FN diameters was not established among groups, improvement of roundness of FN was confirmed with increase in the numbers of capillary in FN-innervated gastrocnemius; additionally, degenerative neuropathy was significantly improved. Importantly, the functional study of electroneurogram (ENG) showed that, slowed conduction of FN in model rats was significantly restored by hMSCs-CU treatment. These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.

Keywords: Diabetic foot; Electroneurogram; Human mesenchymal stem cells from umbilical cord matrix; NGF; Neurofilament; Peripheral neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Foot / pathology
  • Diabetic Foot / physiopathology
  • Diabetic Foot / therapy*
  • Femoral Nerve / metabolism
  • Femoral Nerve / pathology*
  • Femoral Nerve / physiopathology
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / innervation
  • Neovascularization, Physiologic
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / therapy*
  • Nerve Growth Factor / blood
  • Neural Conduction
  • Neurofilament Proteins / metabolism
  • Neurons / metabolism
  • Rats, Sprague-Dawley

Substances

  • Neurofilament Proteins
  • neurofilament protein H
  • Nerve Growth Factor