Peripheral nerve repair of transplanted undifferentiated adipose tissue-derived stem cells in a biodegradable reinforced nerve conduit

J Biomed Mater Res A. 2012 Jan;100(1):48-63. doi: 10.1002/jbm.a.33227. Epub 2011 Oct 4.

Abstract

This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an improved approach to patient care.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Biocompatible Materials / pharmacology*
  • Biodegradation, Environmental / drug effects
  • Calcium Phosphates / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Electrophysiological Phenomena / drug effects
  • Gelatin / pharmacology
  • Iridoids / pharmacology
  • Male
  • Microscopy, Electron, Scanning
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology*
  • Sciatic Nerve / physiopathology
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Sus scrofa
  • Tissue Scaffolds / chemistry*
  • Wound Healing / drug effects*

Substances

  • Biocompatible Materials
  • Calcium Phosphates
  • Iridoids
  • Gelatin
  • genipin
  • tricalcium phosphate