2006 Fiscal Year Final Research Report Summary
Investigation of neutralizing and neurotrophic effects of bone marrow stromal cells
| Project/Area Number |
16591456
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
NAKAO Naoyuki Wakayama Medical University, Neurosurgery, Associate Prof., 医学部, 講師 (30301435)
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| Co-Investigator(Kenkyū-buntansha) |
ITAKURA Toru Wakayama Medical University, Neurosurgery, Prof., 医学部, 教授 (40100995)
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| Project Period (FY) |
2004 – 2006
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| Keywords | cell transplantation / ES cells / Dopamine neurons |
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| Research Abstract |
The general aim of the present research project is to investigate whether bone marrow stromal cells may provide neurotrophic and neutralizing effects. The results can be summarized as follows.
1. Neurotrophic effects: Bone marrow stromal cells (BMSC) were obtained from the mouse femur, and grown under serum-free culture conditions. After BMSC were incubated for 24 hrs, the supernatant was collected and served as BMSC-derived conditioned medium (CM). Incubation with BMSC-derived CM significantly promoted the survival of cultured tyrosine hydroxylase (TH)-positive dopamine (DA) neurons that otherwise died with time in vitro under serum-free culture conditions. BMSC-derived CM was also found to prevent the neurotoxin 6-OHDA-induced death of TH-positive DA cells in vitro. We also examined whether BMSC-derived CM may promote the survival of embryonic DA neurons grafted into the stratum of a rat model of Parkinson's disease. Treatment of donor cells with the CM significantly enhanced the surv
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ival of grafted TH-positive DA cells with a more rapid recovery of motor deficits noted in the rat disease model. Quantification of protein levels in BMSC-derived CM by using ELISA detected FGF-2, BDNF and GDNF, all of which have been shown to exhibit trophic effects on DA neurons.
2. Neutralizing effects: Embryonic stem (ES) cells that are clonal cell lines derived from the inner cell mass of the developing blastcytes have the ability of proliferating extensively in vitro and of generating any cell types of the three embryonic germ layers. When ES cells were incubated on BMSC feeder layers in erum-free N2 medium for 5 days, more than 90% of the cells were found to express the neuronal marker TuJ1. By contrast, only 10% of the cells were positive for TuJ1 after they were grown on poly-D-lysin-coated culture dishes in serum-free N2 medium alone for 5 days.
In conclusion, the present study indicates that BMSC-derived CM contains diffusible factors capable of exerting neurotrophic and neutralizing effects. Less
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