Possible use of autologous stem cell therapies for Alzheimer's disease.
Possible use of autologous stem cell therapies for Alzheimer's disease.
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DOI：
10.2174/1567205054367919
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发表时间：
2005-06
影响因子：
2.1
通讯作者：
K. Sugaya
中科院分区：
文献类型：
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作者：
K. Sugaya
“神经退行性疾病是无法治愈的，因为神经元在成年期不会再生”的说法受到了挑战，我们现在已经发现了许多证据表明成熟的大脑能够再生神经元。在我们之前的研究中，将人神经干细胞（HNSCs）移植到老年大鼠脑中分化为神经细胞，并显着改善动物的认知功能，表明HNSCs可能是神经替代治疗的有希望的候选者。然而，由于与HNSCs相关的伦理和实践问题，可能需要开发自体干细胞策略。我们建立了通过改变细胞命运决定将成人间充质干细胞分化为神经细胞的新技术。我们还发现了嘧啶衍生物，增加内源性干细胞增殖和神经发生后，外周给药这种化合物。尽管这些结果可能为干细胞策略在阿尔茨海默病（AD）治疗中的临床应用带来光明的前景，但我们必须承认AD的复杂性。例如，淀粉样β前体蛋白（APP）的异常代谢可能会影响干细胞生物学，而淀粉样β肽（Abeta）毒性理论在AD病理学中的流行往往限制了我们对APP生理功能的关注。即使神经胶质活化可用于消除Abeta沉积物，但需要干细胞的神经元分化来替换AD脑中的退化神经元。因此，需要进一步研究AD病理学对干细胞生物学的影响。
The statement, "neurodegenerative diseases are incurable because neurons do not regenerate during adulthood," has been challenged, and we have now found much evidence that the matured brain is capable of regenerating neurons. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for neuro-replacement therapy. However, because of ethical and practical issues associated with HNSCs, development of autologous stem cell strategies may be desired. We established new technologies to differentiate adult human mesenchymal stem cells into neural cells by modifying cell fate decisions. We also found a pyrimidine derivative that increases endogenous stem cell proliferation and neurogenesis after peripheral administrations of this compound. Although these results may promise a bright future for clinical applications of stem cell strategies in Alzheimer's disease (AD) therapy, we must acknowledge the complexity of AD. For example, abnormal metabolism of the amyloid-beta precursor protein (APP) may affect stem cell biology, while the prevalence of amyloid-beta peptide (Abeta) toxicity theory in AD pathology tends to limit our focus on the physiological functions of APP. We found that excess APP in the environment causes glial differentiation of stem cells. Even though the glial activation may be useful to eliminate Abeta deposits, neuronal differentiation of stem cells is needed for replacement of degenerating neurons in the AD brain. Thus, further investigation of the influence of AD pathology on stem cell biology is required.