Sensory & Motor System Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Int J Mol Sci. 2021 Jan 30;22(3):1404. doi: 10.3390/ijms22031404.
Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To treat them, regenerative therapies using skeletal cells have been an attractive choice for patients with unmet clinical needs. Currently, there are two major strategies to prepare the cell sources. The first is to use induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), which can recapitulate the skeletal developmental process and differentiate into various skeletal cells. Skeletal tissues are derived from three distinct origins: the neural crest, paraxial mesoderm, and lateral plate mesoderm. Thus, various protocols have been proposed to recapitulate the sequential process of skeletal development. The second strategy is to extract stem cells from skeletal tissues. In addition to mesenchymal stem/stromal cells (MSCs), multiple cell types have been identified as alternative cell sources. These cells have distinct multipotent properties allowing them to differentiate into skeletal cells and various potential applications for skeletal regeneration. In this review, we summarize state-of-the-art research in stem cell differentiation based on the understanding of embryogenic skeletal development and stem cells existing in skeletal tissues. We then discuss the potential applications of these cell types for regenerative medicine.
骨骼疾病，如骨关节炎和骨折，是影响老年人生活质量的主要疾病之一。为了治疗这些疾病，利用骨骼细胞的再生疗法一直是临床需求未得到满足的患者的一个有吸引力的选择。目前，有两种主要的策略来准备细胞来源。第一种是使用诱导多能干细胞（iPSCs）或胚胎干细胞（ESCs），它们可以重现骨骼发育过程，并分化为各种骨骼细胞。骨骼组织来源于三个不同的起源：神经嵴、轴旁中胚层和侧板中胚层。因此，已经提出了多种方案来重现骨骼发育的顺序过程。第二种策略是从骨骼组织中提取干细胞。除了间充质干细胞（MSCs）外，还鉴定出多种细胞类型作为替代细胞来源。这些细胞具有不同的多能性特征，允许它们分化为骨骼细胞，并具有多种潜在的骨骼再生应用。在这篇综述中，我们总结了基于对胚胎骨骼发育和骨骼组织中存在的干细胞的理解的基于干细胞分化的最新研究。然后，我们讨论了这些细胞类型在再生医学中的潜在应用。
