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

• Published in: Neural regeneration research Vol. 10; no. 6; pp. 850 - 858
• Main Authors: Castorina, Alessandro, Szychlinska, Marta Anna, Marzagalli, Rubina, Musumeci, Giuseppe
• Format: Journal Article
• Language: English
• Published: India Medknow Publications & Media Pvt. Ltd 01.06.2015; Department of Biomedical and Biotechnological Science, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Soifa 87, Catania, Italy; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Age; Aging; Apoptosis; axon; Binding sites; Biomarkers; Cell growth; cellular therapy; Dementia; Deoxyribonucleic acid; Disease; DNA; DNA methylation; DNA repair; Eg5; Enzymes; Homeostasis; Invited Review; kinesin-5; microtubule; molecular motor protein; monastrol; MSCs; Mutation; Neurodegeneration; neurodegenerative disorders; Oxidative stress; Proteins; regeneration; Senescence; Stem cells; Telomerase; telomere shortening; 中枢神经系统; 再生能力; 基础; 延缓衰老; 治疗; 神经退行性疾病; 自我修复能力; 骨髓间充质干细胞; telomere shortening; MSCs; aging; cellular therapy; neurodegenerative disorders
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.158352

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 longterm 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-re- lated 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.