Markers for the identification of tendon-derived stem cells in vitro and tendon stem cells in situ - update and future development.

Pauline Po Yee Lui

doi:10.1186/s13287-015-0097-y

Abstract

The efficacy of tendon-derived stem cells (TDSCs) for the promotion of tendon and tendon-bone junction repair has been reported in animal studies. Modulation of the tendon stem cell niche in vivo has also been reported to influence tendon structure. There is a need to have specific and reliable markers that can define TDSCs in vitro and tendon stem cells in situ for several reasons: to understand the basic biology of TDSCs and their subpopulations in vitro; to understand the identity, niches and functions of tendon/progenitor stem cells in vivo; to meet the governmental regulatory requirements for quality of TDSCs when translating the exciting preclinical findings into clinical trial/practice; and to develop new treatment strategies for mobilizing endogenous stem/progenitor cells in tendon. TDSCs were reported to express the common mesenchymal stem cell (MSC) markers and some embryonic stem cell (ESC) markers, and there were attempts to use these markers to label tendon stem cells in situ. Are these stem cell markers useful for the identification of TDSCs in vitro and tracking of tendon stem cells in situ? This review aims to discuss the values of the panel of MSC, ESC and tendon-related markers for the identification of TDSCs in vitro. Important factors influencing marker expression by TDSCs are discussed. The usefulness and limitations of the panel of MSC, ESC and tendon-related markers for tracking stem cells in tendon, especially tendon stem cells, in situ are then reviewed. Future research directions are proposed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0097-y) contains supplementary material, which is available to authorized users.

Highlights

The efficacy of tendon-derived stem cells (TDSCs) for the promotion of tendon and tendon-bone junction repair has been reported in animal studies
Another study has shown that the surface expression of CD44, CD73, CD90 and CD105 in human TDSCs was maintained under hypoxia (2 % oxygen) as shown by flow cytometry [40]. 2-Mercaptoethanol was added to the initial cell culture for TDSC isolation in some studies [3, 11, 30]. 2-Mercaptoethanol has been reported to improve the culture environment by reducing reactive oxygen species and to promote cell growth by reducing cystine to cysteine needed for cell growth [41]
Many of the existing markers seen as defining mesenchymal stem cell (MSC) are widely shared and expressed by fibroblasts, and these markers do not imply any true in vivo stem cell property that defines true stem cells

Summary

Introduction

The efficacy of tendon-derived stem cells (TDSCs) for the promotion of tendon and tendon-bone junction repair has been reported in animal studies. Despite being heterogeneous cell populations, there is a huge need for markers to characterize and define the biological characteristics of tendon-derived stem cells (TDSCs) or their subpopulations in vitro, and to study the identity, niches and functions of stem/progenitor cells in tendon in vivo. This information is crucial for understanding the molecular/cellular mechanisms of tendon physiology and pathologies, and developing effective treatment strategies. Markers characterizing tendon-derived stem cells in vitro The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy has proposed three minimal criteria to define human mesenchymal stem cells (MSCs). We do not know the point at which the expression of tenogenic markers alone is associated with the loss of self-renewal and multipotency – the definition of terminal differentiation

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