Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats

Neurosurgery. 2005 Nov;57(5):1026-31; discussion 1026-31. doi: 10.1227/01.neu.0000181369.76323.50.

Abstract

Objective: This study was designed to investigate the effects of human bone marrow stromal cell (hMSC) administration in rats for 3 months after traumatic brain injury (TBI).

Methods: Adult male Wistar rats (n = 60) were injured with controlled cortical impact and divided into four groups. The three treatment groups (n = 10 each) were injected with 2 x 10, 4 x 10, and 8 x 10 hMSCs, respectively, intravenously, whereas the control group (n = 30) received phosphate-buffered saline. All injections were performed 1 day after injury into the tail veins of rats. Neurological functional evaluation of animals was performed before and after injury by use of Neurological Severity Scores. Animals were sacrificed 3 months after TBI, and brain sections were stained by immunohistochemistry.

Results: Statistically significant improvement in functional outcome was observed in all three treatment groups compared with control values (P < 0.05). This benefit was visible 14 days after TBI and persisted until 3 months (end of trial). There was no difference in functional outcome among the three treatment groups. Histological analysis showed that hMSCs were present in the lesion boundary zone at 3 months with all three doses tested.

Conclusion: hMSCs injected in rats after TBI survive until 3 months and provide long-lasting functional benefit. Functional improvement may be attributed to stimulation of endogenous neurorestorative functions such as neurogenesis and synaptogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology*
  • Bone Marrow Transplantation / methods*
  • Brain Injuries / physiopathology
  • Brain Injuries / surgery*
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Indoles
  • Male
  • Motor Activity / physiology
  • Neurologic Examination / methods
  • Nuclear Proteins / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Wistar
  • Recovery of Function / physiology*
  • Stromal Cells / physiology*
  • Time Factors

Substances

  • Glial Fibrillary Acidic Protein
  • Indoles
  • Nuclear Proteins
  • DAPI
  • Phosphopyruvate Hydratase