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神经退行性疾病的干细胞治疗。

Stem Cell Therapies for Neurodegenerative Diseases.

机构信息

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.

出版信息

Adv Exp Med Biol. 2018;1056:61-84. doi: 10.1007/978-3-319-74470-4_5.

Abstract

Stem cell therapies have been proposed as a treatment option for neurodegenerative diseases, but the best stem cell source and therapeutic efficacy for neuroregeneration remain uncertain. Embryonic stem cells (ESCs) and neural stem cells (NSCs), which can efficiently generate neural cells, could be good candidates but they pose ethical and practical issues. Not only difficult to find the good source of those cells but also they alway pose immunorejection problem since they may not be an autologous cells. Even if we overcome the immunorejection problem, it has also been reported that transplantation of ESCs develop teratoma. Although adult stem cells are more accessible, they have a limited developmental potential. We developed technologies to increase potency of mesenchymal stem cells, which allow them to develop into neural cells, by over expression of the ESC gene, nanog. We also developed a small molecule compound, which significantly increases endogenous NSCs by peripheral administration, eliminating even the necessity of stem cell injection to the brain. These novel technologies may offer neuroregenerative therapies for Alzheimers disease (AD). However, we found that AD pathological condition prevent neurogenesis from NSCs. This chapter discusses how to overcome the problem associated stem cell therapy under AD pathology and introduces exosome as a tool to improve the modification of adult stem cells. These new technologies may open a door for the new era for AD therapy.

摘要

干细胞疗法被提议作为治疗神经退行性疾病的一种选择,但最佳的干细胞来源和神经再生的治疗效果仍不确定。胚胎干细胞 (ESCs) 和神经干细胞 (NSCs) 可以有效地产生神经细胞,可能是很好的候选者,但它们存在伦理和实际问题。不仅难以找到这些细胞的良好来源,而且由于它们可能不是自体细胞,因此始终存在免疫排斥问题。即使我们克服了免疫排斥问题,也有报道称 ESC 移植会发展为畸胎瘤。虽然成体干细胞更容易获得,但它们的发育潜力有限。我们开发了通过过表达 ESC 基因 Nanog 来增加间充质干细胞向神经细胞分化能力的技术。我们还开发了一种小分子化合物,通过外周给药可显著增加内源性 NSCs,甚至消除了将干细胞注射到大脑的必要性。这些新技术可能为阿尔茨海默病 (AD) 提供神经再生疗法。然而,我们发现 AD 病理状况阻止了 NSCs 的神经发生。本章讨论了如何克服 AD 病理相关的干细胞治疗问题,并介绍了外泌体作为一种改善成体干细胞修饰的工具。这些新技术可能为 AD 治疗的新时代开辟了一扇大门。

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