Department of Surgery and Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4N1, Canada.
McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2022 May 14;23(10):5496. doi: 10.3390/ijms23105496.
Adult mesenchymal stem cells were reported more than 30 years ago. Since then, their potential to repair and regenerate damaged or diseased tissues has been studied intensively in both preclinical models and human trials. Most of the need for such tissue repair/regeneration is in older populations, so much of the effort has been performed with autologous cells in older patients. However, success has been difficult to achieve. In the literature, it has been noted that such progenitor cells from younger individuals often behave with more vigorous activity and are functionally enhanced compared to those from older individuals or animals. In addition, cells with the characteristics of mesenchymal stem cells or pluripotent mesenchymal regulatory cells exist in nearly all tissues and organs as pericytes since fetal life. Such evidence raises the possibility that one of the primary roles of these organ-specific cells is to regulate organ growth and maturation, and then subsequently play a role in the maintenance of organ integrity. This review will discuss the evidence to support this concept and the implications of such a concept regarding the use of these progenitor cells for the repair and regeneration of tissues damaged by injury or disease later in life. For the latter, it may be necessary to return the organ-specific progenitor cells to the functional state that contributed to their effectiveness during growth and maturation rather than attempting to use them after alterations imposed during the aging process have been established and their function compromised.
成人间充质干细胞在 30 多年前就有报道。从那时起,人们就在临床前模型和人体试验中对其修复和再生受损或患病组织的潜力进行了深入研究。这种组织修复/再生的大部分需求都在老年人群中,因此,在老年患者中,大量使用的是自体细胞。然而,取得的成功却难以实现。在文献中,人们注意到,与来自老年个体或动物的细胞相比,来自年轻个体的这种祖细胞通常表现出更活跃的活性和更强的功能。此外,自从胎儿期起,几乎所有的组织和器官中都存在具有间充质干细胞或多能间充质调节细胞特征的细胞,作为周细胞存在。这种证据提出了这样一种可能性,即这些器官特异性细胞的主要作用之一可能是调节器官的生长和成熟,然后在维持器官完整性方面发挥作用。本综述将讨论支持这一概念的证据,以及这一概念对利用这些祖细胞修复和再生因损伤或疾病而受损组织的影响。对于后者,可能有必要使器官特异性祖细胞恢复到在生长和成熟过程中发挥作用的功能状态,而不是在衰老过程中已经建立并损害其功能的改变之后尝试使用它们。