The Progress of Stem Cell Technology for Skeletal Regeneration

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.

Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors

“…As it is currently possible to generate LPM and PXM precursors from induced pluripotent stem (iPS) cells (Matsuda et al, 2020;Nazareth et al, 2013;Tani et al, 2021), we envisage the possibility of using iPS cells as a source of stromal progenitors to further investigate the molecular factors involved in stromal cell fate decision and, more generally, in lymphoid stromagenesis. Given the critical role of stromal and endothelial progenitor cells in the organization of the lymphoid compartment, we hypothesize that iPS-derived stromal progenitor cells could be used in the context of immune engineering for the development of functional artificial lympho-organoids to replace LN and restore lymphoid and immunological functions in various diseases in which LN has been resected or dysfunctional, such as cancer, infections, and lymphedema (Dijkstra et al, 2018;Kim et al, 2019;Kobayashi and Watanabe, 2016;Lenti et al, 2019).…”

How the mechanical microenvironment of stem cell growth affects their differentiation: a review

“…Therefore, the application of stem cells in the field of osteoarthritis treatment is of interest. However, further integration and analysis of the efficacy and safety of stem cell therapy are still needed [ 129 ], and more research is needed. More types of stem cells are being studied which hold great promise for therapeutic use [ 130 ].…”

Cilia kinases in skeletal development and homeostasis

“…318 The cilia signaling thus contributes to the development and homeostasis of the skeleton, among other mechanisms, through regulating cell fate decisions of the skeletal stem cells. Importantly, the recently identified skeletal progenitors may contribute to the development of novel therapies for large skeletal defects, 319,320 by activation of the quiescent stem cells, 305,306 or allogeneic cell therapy in the genetic skeletal disorders including ciliopathies.…”