Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats: secretion of neurotrophic factors and inhibition of apoptosis.
To investigate the therapeutic effects and mechanisms of action of human mesenchymal stem cells (hMSCs), rats were intravenously treated with hMSCs 24 h after traumatic brain injury (TBI). Neurological function was significantly recovered in the hMSC-treated group by 15 days after TBI compared to the placebo group treated with saline. Quantitative ELISA of extracts from the entire traumatized cerebral hemispheres showed significantly increased expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) in the hMSC group at 2 days after TBI, with expression decreasing over time. Western blot analysis demonstrated that pAkt expression was upregulated at 2 days after TBI, and caspase-3 cleavage was significantly decreased at 8 days after TBI in the hMSC group. Our results show that treatment of TBI with hMSCs during the acute phase of injury can enhance neurological functional outcome, and suggest that increased levels of neurotrophic factors in the injured hemisphere leading to decreased neuronal apoptosis is one mechanism by which functional recovery may occur.
Kim
Hwa-Jung
HJ
Department of Neurosurgery, Ajou University School of Medicine, Yeongtong-Gu, Suwon, Korea.
Lee
Jae-Ho
JH
Kim
Se-Hyuk
SH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D054022:Cerebrum / Q000293:injuries / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous / Q000379:methods; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3