Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats

J Transl Med. 2010 Jun 28:8:63. doi: 10.1186/1479-5876-8-63.

Abstract

Background: The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.

Methods: Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.

Results: The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).

Conclusions: ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Apoptosis / genetics
  • Brain Infarction / metabolism
  • Brain Infarction / pathology
  • Brain Infarction / physiopathology*
  • Brain Infarction / therapy*
  • Cell Count
  • Doublecortin Protein
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / metabolism
  • Indoles / metabolism
  • Inflammation / complications
  • Inflammation / genetics
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Neovascularization, Physiologic
  • Neurogenesis
  • Oxidative Stress / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transplantation, Autologous
  • von Willebrand Factor / metabolism

Substances

  • Dcx protein, rat
  • Doublecortin Protein
  • Glial Fibrillary Acidic Protein
  • Indoles
  • RNA, Messenger
  • von Willebrand Factor
  • DAPI