中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 850-858.doi: 10.4103/1673-5374.158352

• 综述:退行性病与再生 • 上一篇    下一篇

间充质干细胞对神经退行性疾病的潜在治疗:答案是逃逸衰老吗?

  

  • 收稿日期:2015-04-10 出版日期:2015-06-18 发布日期:2015-06-18

Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders: is the escape from senescence an answer?

Alessandro Castorina, Marta Anna Szychlinska, Rubina Marzagalli, Giuseppe Musumeci   

  1. Department of Biomedical and Biotechnological Science, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, Catania, Italy
  • Received:2015-04-10 Online:2015-06-18 Published:2015-06-18
  • Contact: Alessandro Castorina, M.S., Ph.D.,alecasto@unict.it.
  • Supported by:

    This study was in part supported by the Department of Biomedical Sciences and Biotechnologies, Medical School, University of Catania, Italy (National Grant. PON 01_00110).

摘要:

衰老是神经退行性疾病发展的最突出风险因素。在美国,超过3500万的老年人患有老年性疾病。老化会损害神经细胞的自我修复能力,而这一过程会持续恶化。退化一旦发生,就会阻碍本已有限的中枢神经系统再生能力,并且很难寻找新的治疗策略。目前,间充质干细胞已被证明是改善神经退变的一个可行选择,因为它们在体外的多个谱系均具有高增殖率和分化率。然而,已有研究表明长期培养的间充质干细胞会进行自发转化,转化的干细胞显示出衰老的典型特征。一些证据表明衰老可能是限制干细胞治疗开发的主要因素,这促使学者们寻找多能细胞的替代来源,或是阻止与年龄有关的细胞老化。

Abstract:

Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration.Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during long-term culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-related transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.

Key words: aging, neurodegenerative disorders, telomere shortening, MSCs, cellular therapy