1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.
2 Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, United Kingdom.
Cell Transplant. 2017 Sep;26(9):1520-1529. doi: 10.1177/0963689717721201.
Aging at the cellular level is a complex process resulting from accumulation of various damages leading to functional impairment and a reduced quality of life at the level of the organism. With a rise in the elderly population, the worldwide incidence of osteoporosis (OP) and osteoarthritis (OA) has increased in the past few decades. A decline in the number and "fitness" of mesenchymal stromal cells (MSCs) in the bone marrow (BM) niche has been suggested as one of the factors contributing to bone abnormalities in OP and OA. It is well recognized that MSCs in vitro acquire culture-induced aging features such as gradual telomere shortening, increased numbers of senescent cells, and reduced resistance to oxidative stress as a result of serial population doublings. In contrast, there is only limited evidence that human BM-MSCs "age" similarly in vivo. This review compares the various aspects of in vitro and in vivo MSC aging and suggests how our current knowledge on rejuvenating cultured MSCs could be applied to develop future strategies to target altered bone formation processes in OP and OA.
细胞水平的衰老过程是一个复杂的过程,是各种损伤累积导致的功能障碍和机体水平生活质量下降的结果。随着老年人口的增加,过去几十年,全世界骨质疏松症 (OP) 和骨关节炎 (OA) 的发病率都有所上升。骨髓 (BM) 龛中间充质基质细胞 (MSCs) 的数量和“功能”下降被认为是导致 OP 和 OA 骨骼异常的因素之一。人们已经认识到,体外 MSC 获得了培养诱导的衰老特征,例如端粒逐渐缩短、衰老细胞数量增加以及由于连续传代而对氧化应激的抵抗力降低。相比之下,仅有有限的证据表明,人体内 BM-MSCs 会在体内以类似的方式“衰老”。这篇综述比较了体外和体内 MSC 衰老的各个方面,并提出了如何将我们目前关于培养 MSC 年轻化的知识应用于开发未来的策略,以针对 OP 和 OA 中改变的骨形成过程。