Protection of dopamine neurons by bone marrow stromal cells.
Transplantation of bone marrow stromal cells (BMSC) has recently been demonstrated to provide neuroprotection in animal models of brain injuries such as ischemia and trauma. The present study was undertaken to explore whether BMSC can promote the survival of dopamine (DA) neurons in neuronal insult models in vitro. We also examined whether BMSC can increase the survival rate of embryonic DA neurons grafted into the striatum of a rat model of Parkinson's disease (PD). Treatment with conditioned media derived from BMSC cultures was found to significantly prevent the death of DA neurons in in vitro cell injury models such as serum deprivation and exposure to the neurotoxin 6-OHDA. In a transplantation study, we also found that the survival of grafted DA cells was significantly enhanced by treating donor cells with the conditioned media at the steps of both cell dissociation and implantation. The results suggest that BMSC may secrete diffusible factors able to protect DA neurons against neuronal injuries. Indeed, BMSC expressed mRNA encoding brain-derived neurotrophic factor, fibroblast growth factor-2 and glial cell line-derived neurotrophic factor, all of which have previously been shown to exhibit potent neurotrophic effects on DA cells. Enzyme-linked immunosorbent assay revealed that the cells release these growth factors into culture media. The present data indicate that BMSC may be a potential donor source of cell-based regenerative therapy for PD where the progressive loss of the midbrain DA neurons takes place.
Shintani
Aki
A
Department of Neurological Surgery, Wakayama Medical University, Wakayama, Japan.
Nakao
Naoyuki
N
Kakishita
Koji
K
Itakura
Toru
T
D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016380:Brain Tissue Transplantation; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D006085:Graft Survival / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D051379:Mice; D017072:Neostriatum / Q000166:cytology / Q000601:surgery*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000473:pathology / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D001685:Biological Factors; D017077:Culture Media, Conditioned; D004298:Dopamine