Development of pluripotent stem cell‐based human tenocytes

Abstract

Human pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for studying PSCs is to understand human embryogenesis and development. All cell types that make up the body tissues develop through defined trajectories during embryogenesis. For example, paraxial mesoderm is considered to differentiate into several cell types including skeletal muscle cells, chondrocytes, osteocytes, dermal fibroblasts, and tenocytes. Tenocytes are fibroblast cells that constitute the tendon. The step‐wise narrowing fate decisions of paraxial mesoderm in the embryo have been modeled in vitro using PSCs; however, deriving tenocytes from human‐induced PSCs and their application in cell therapy have long been challenging. PSC‐derived tenocytes can be used for a source of cell transplantation to treat a damaged or ruptured tendon due to injury, disorder, or aging. In this review, we discuss the latest research findings on the use of PSCs for studying the biology of tenocyte development and their application in therapeutic settings.

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture

“…The dorsal part of the sclerotome further differentiates into the syndetome, which eventually gives rise to tenocytes in the torso 24,29 . This step-wise narrowing fate decision of the paraxial mesoderm in the embryo can be recapitulated in vitro with PSCs, such as iPSCs or embryonic stem cells [13][14][15][30][31][32][33][34] . We have previously demonstrated the directed differentiation of tenocytes from human iPSCs by modeling human somite development in vitro [13][14][15] .…”

“…This step-wise narrowing fate decision of the paraxial mesoderm in the embryo can be recapitulated in vitro with PSCs, such as iPSCs or embryonic stem cells [13][14][15][30][31][32][33][34] . We have previously demonstrated the directed differentiation of tenocytes from human iPSCs by modeling human somite development in vitro [13][14][15] . Here, we modified our conventional protocols to establish a method to robustly derive tenocytes from human iPSCs in xenofree conditions using an iPSC line, 1231A3 35 .…”

“…Therefore, there is a considerable demand for novel technology-based cell therapies for treating tendon injury. We have been developing an induced pluripotent stem cell (iPSC)based technology and reported the first method for inducing differentiation of iPSC-derived tenocytes (iPSC-tenocytes) that could potentially be applied to transplantation therapy [13][14][15] . Utilizing terminally differentiated iPSC-tenocytes is promising as it avoids ethical concerns and autologous tissue harvest and because of the high proliferative ability and relatively low risk of ectopic tissue formation 11 .…”

Application of Stem Cell Therapy for ACL Graft Regeneration

“…Learning from embryonic tendon development can improve tendon tissue engineering strategies with adult stem cells, and tenogenic cues and markers will need to be established for step-wise induction [ 132 ]. Some studies have delivered MSCs together with exogenous proteinogenic growth factors to induce tenogenic differentiation.…”

Pluripotent stem cells in developmental biology

“…(2021) summarize the research history of molecular mechanisms of neural development and review how its findings have been applied to neural induction and differentiation from PSCs, as well as the application to disease models. Nakajima and Ikeya (2021) discuss the latest research findings on how to induce tendon cells from PSCs and the possibility of future medical applications. In Section 3, Thompson and Takebe (2021) review the induction of 3D liver organoids from human PSCs, which has evolved rapidly in recent years.…”