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體外培養之胚胎中腦細胞在巴金森氏症神經移植治療的應用
Possible Applications of Cultured Embryonic Mesencephalic Cells for the Treatment of Parkinson's Disease
摘要
臨床研究顯示在患者紋狀體中移植胚胎黑質組織以取代退化的多巴胺神經元，在巴金森氏症的治療上非常具有潛力。由於胚胎來源不易、移植組織的免疫排斥反應與存活等問題，胚胎黑質組織移植在治療上的應用仍受到許多限制，有待研究改善；因此學者嘗試於體外培養可長期存活的多巴胺神經元。1982年，Berger等學者報告小鼠13天胚胎的中腦細胞在體外，可於補充血清的培養液中存活達6週；1993年，Spector等學者發現多巴胺神經元前驅細胞與豬神經上皮共同培養時可繼續增生；而Clarkson等學者進一步報告神經滋養因子可抑制體外培養之多巴胺神經元的細胞凋亡，而增進其存活。本實驗室最近以ICR小鼠14-17天胚胎的中腦細胞進行培養；結果顯示小鼠胚胎中腦的多巴胺神經細胞和神經膠質細胞在體外共同培養時，可能經由GDNF等神經滋養因子維持及調控多巴胺神經細胞增生及分化；因此在體外培養中，可續代培養16代以上，仍無明顯老化及凋亡的情形。由於本實驗室所建立的中腦細胞體外培養模式，除了可在體外大量培養外；並可分泌GDNF等神經滋養因子以增進移植後多巴胺神經元的存活，又不牽涉到倫理及法律的問題，因此在巴金森氏症的神經移植治療上非常具有潛力。
並列摘要
Intrastriatal transplantation of embryonic neural tissue to replace degenerated dopaminergic neurons is shown to be a potential treatment for Parkinson's disease (Kordower et al., 1995). However, the potential of neurotransplantation is restricted by immunological rejection, source and survival of the neural tissue. In order to develop the source and improve the survival of neural tissue, long-time survival mesencephalic cells has been trying to establish. In 1982, Berger and his colleagues showed that mesencephalic cells from 13-days-old mouse embryos might be cultured in a serum-complemented medium up to six weeks. Dopamine-neuronal precursor cells continued to divide in porcine neuroepithelial culture (Spector et al., 1993). In addition, GDNF reduces apoptosis and improves the survival of human embryonic dopaminergic neurons in vitro (Clarkson et al, 1997). In recent studies, we shown that dopaminergic neurons and neuralgia recovered from 14-17 day-embryo of ICR mouse, might secret neurotrophic factors such as GDNF to promote survival and modulate differentiation of dopaminergic neurons in vitro though 16 passages. The co-culture of dopaminergic neurons and neuroglia may be a ideal model to generate functional dopaminergic neurons in vitro for neurotransplantation in Parkinson's disease.
延伸閱讀
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