Abstract
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.
Highlights
Skeletal disorders, such as osteoarthritis and bone fractures, cause critical deformation and dysfunctions in skeletal tissues, resulting in a compromised quality of life, especially in elderly individuals [1,2]
Several protocols have been proposed for the stepwise induction of osteoblasts from the mesoderm or sclerotome derived from hPSCs and mouse PSCs (mPSCs) [6,15,22,41,42]
Because limb bud-derived skeletal tissues are often related to skeletal diseases, including osteoarthritis and bone fracture [1], generating the “on-site” cell sources derived from lateral plate mesoderm may be promising
Summary
Skeletal disorders, such as osteoarthritis and bone fractures, cause critical deformation and dysfunctions in skeletal tissues, resulting in a compromised quality of life, especially in elderly individuals [1,2]. The of second strategy is to use stem cells purified from adult skeletal tissues. Multiple cell cell types including skeletal stem and applied appliedto toclinical clinicalsettings settings[10]. Multiple types including skeletal cells (SSCs) and CXCL12-abundant reticular (CAR). Cells have been identified as cell stem cells (SSCs) and CXCL12-abundant reticular (CAR) cells have been identified aspopcell ulations withwith unique properties and potentials. Cells distinct have distinct multipotent erties which allowallow them them to differentiate into several skeletal cell types. We first summarize the current understanding of skeletal development in embryos this review, we first summarize the current understanding of skeletal development in and the induction protocols protocols for recapitulating the developmental process with stem cells. ESC, embryonic stem/stromal cell; SSC, skeletal stem cell.
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