Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
Stem Cells Transl Med. 2012 Sep;1(9):651-7. doi: 10.5966/sctm.2012-0033. Epub 2012 Sep 5.
Self-renewal and multilineage differentiation of stem cells are keys to the lifelong homeostatic maintenance of tissues and organs. Hematopoietic aging, characterized by immunosenescence, proinflammation, and anemia, is attributed to age-associated changes in the number and function of hematopoietic stem cells (HSCs) and their microenvironmental niche. Genetic variants and factors regulating stem cell aging are correlatively or causatively associated with overall organismal aging and longevity. Translational use of HSCs for transplantation and gene therapy demands effective methods for stem cell expansion. Targeting the molecular pathways involved in HSC self-renewal, proliferation, and homing has led to enhanced expansion and engraftment of stem cells upon transplantation. HSC transplantation is less effective in elderly people, even though this is the demographic with the greatest need for this form of treatment. Thus, understanding the biological changes in the aging of stem cells as well as local and systematic environments will improve the efficacy of aged stem cells for regenerative medicine and ultimately facilitate improved health and life spans.
干细胞的自我更新和多能性分化是组织和器官终身维持体内平衡的关键。造血衰老的特征是免疫衰老、炎症前状态和贫血,这归因于造血干细胞(HSCs)及其微环境龛数量和功能的年龄相关变化。调节干细胞衰老的遗传变异和因素与整体机体衰老和长寿呈相关性或因果关系。HSCs 用于移植和基因治疗的转化应用需要有效的干细胞扩增方法。针对 HSC 自我更新、增殖和归巢涉及的分子途径的靶向治疗已导致移植后干细胞的扩增和植入增强。HSC 移植在老年人中效果较差,尽管这是最需要这种治疗形式的人群。因此,了解衰老的干细胞以及局部和系统环境中的生物学变化将提高老年干细胞在再生医学中的功效,并最终促进健康和寿命的延长。