Tendon Stem/Progenitor Cell Subpopulations and Their Implications in Tendon Biology.

Zizhan Huang,Yang Fei,Zi Yin,Jialu Xu,Xuesheng Jiang,Boon Chin Heng,Weishan Chen,Weiliang Shen

doi:10.3389/fcell.2021.631272

Abstract

Tendon harbors a cell population that possesses stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity, commonly referred to as tendon stem/progenitor cells (TSPCs). Various techniques have been employed to study how TSPCs are implicated in tendon development, homeostasis and healing. Recent advances in single-cell analysis have enabled much progress in identifying and characterizing distinct subpopulations of TSPCs, which provides a more comprehensive view of TSPCs function in tendon biology. Understanding the mechanisms of physiological and pathological processes regulated by TSPCs, especially a particular subpopulation, would greatly benefit treatment of diseased tendons. Here, we summarize the current scientific literature on the various subpopulations of TSPCs, and discuss how TSPCs can contribute to tissue homeostasis and pathogenesis, as well as examine the key modulatory signaling pathways that determine stem/progenitor cell state. A better understanding of the roles that TSPCs play in tendon biology may facilitate the development of novel treatment strategies for tendon diseases.

Highlights

Tendon tissues have a hierarchical structure with unique mechanical properties, and serve to connect embryologically distinct musculoskeletal tissues, bone and muscle, and mainly function to transmit mechanical forces to enable skeletal locomotion
An important finding is that a nestin+ subpopulation of tendon stem/progenitor cells (TSPCs), which is more capable of self-renewal and tenogenic differentiation than the nestin− subpopulation, has been identified by single-cell analysis and is involved in the development and endogenous repair of tendon tissues (Yin et al, 2016)
Osteocalcinexpressing cells whose proliferation and differentiation are regulated by Hedgehog (Hh) signaling, have been found in the peritenon, demonstrating stem/progenitor cell properties comparable to TSPCs isolated from the mid-substance (Wang et al, 2017)

Summary

Introduction

Tendon tissues have a hierarchical structure with unique mechanical properties, and serve to connect embryologically distinct musculoskeletal tissues, bone and muscle, and mainly function to transmit mechanical forces to enable skeletal locomotion. Tendon stem cell niche is essential for TSPCs to maintain their properties and determine tenogenic fate.

Results

Conclusion