Intracranial transplantation of human adipose-derived stem cells promotes the expression of neurotrophic factors and nerve repair in rats of cerebral ischemia-reperfusion injury

Int J Clin Exp Pathol. 2013 Dec 15;7(1):174-83. eCollection 2014.

Abstract

Adipose tissue-derived mesenchymal stem cells (ADSCs) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The aim of this study was to investigate whether ADSCs transplantation could promote nerve repair in rats of cerebral ischemia-reperfusion (I/R) injury. We isolated and cultured human ADSCs, and then measured cell surface antigens by flow cytometry and immunofluorescence. Healthy SD rats were randomly divided into sham group, MCAO group, MCAO+vehicle group and MCAO+ADSCs group. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion (MCAO). Then the human ADSCs were transplanted into the brain of rats 24 h after MCAO. The mRNA level of BDNF (brain derived neurotrophic factor, BDNF), NGF (nerve growth factor, NGF) and bFGF (basic fibroblasts growth factor, bFGF) were detected by real-time PCR at different time points (d7, d14, d21 and d28 after MCAO). Meanwhile, the neurological deficit scores were estimated. The neurological deficit of rats in MCAO+ADSCs group attenuated at d7 in contrast to the MCAO+vehicle group (P<0.05). Subsequently, they were dramatically ameliorated with the time especially at d28. At d7, d14, d21 and d28 after ADSCs transplantation, BDNF, NGF and bFGF mRNA in MCAO+ADSCs group were strikingly higher than those in MCAO+vehicle group, and these two groups both reached the peak at d14. The western blotting results showed that BDNF and Bcl-2 expressed higher in MCAO+ADSCs group than MCAO+vehicle group. Therefore, our current results suggest that ADSCs promote nerve repair after injury through elevating the expression of neurotrophic factors and inhibiting the apoptosis of neural cells.

Keywords: Adipose-derived stem cells; BDNF; NGF; bFGF; cerebral ischemia-reperfusion injury; nerve repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / transplantation
  • Adolescent
  • Adult
  • Animals
  • Blotting, Western
  • Brain Ischemia* / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Nerve Growth Factors / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Recovery of Function
  • Reperfusion Injury* / metabolism
  • Young Adult

Substances

  • Nerve Growth Factors