Tendon-Derived Stem Cells (TDSCs): From Basic Science to Potential Roles in Tendon Pathology and Tissue Engineering Applications

Abstract

Traditionally, tendons are considered to only contain tenocytes that are responsible for the maintenance, repair and remodeling of tendons. Stem cells, which are termed tendon-derived stem cells (TDSCs), have recently been identified in tendons. This review aims to summarize the current information about the in vitro characteristics of TDSCs, including issues related to TDSC isolation and culture, their cell morphology, immunophenotypes, proliferation and differentiation characteristics and senescence during in vitro passaging. The challenges in studying the functions of these cells are also discussed. The niche where TDSCs resided essentially provides signals that are conducive to the maintenance of definitive stem cell properties of TDSCs. Yet the niche may also induce pathologies by imposing an aberrant function on TDSCs or other targets. The possible niche factors of TDSCs are herein discussed. We presented current evidences supporting the potential pathogenic role of TDSCs in the development of tendinopathy with reference to the recent findings on the altered biological responses of these cells in response to their potential niche factors. The use of resident stem cells may promote engraftment and differentiation of transplanted cells in tendon and tendon-bone junction repair because the tendon milieu is an ideal and familiar environment to the transplanted cells. Evidences are presented to show the potential advantages and results of using TDSCs as a new cell source for tendon and tendon-bone junction repair. Issues pertaining to the use of TDSCs for tissue repair are also discussed.

In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

“…Several different cell populations reside between chains of these long and parallel fibrils, including tenocytes (Lui, 2013), their precursor cells are called tenoblasts and tendon stem/progenitor cells (Bi et al, 2007;Kannus, 2000). Tenocytes, spindle-shaped and elongated, are the most numerous cell population and they are responsible for the formation/turnover of extracellular matrix, assembly of early collagen fibres and facilitation of collagen network adaptation to external stimuli (Milz et al, 2009).…”

“…Tenoblasts, on the other hand, can vary in size and shape and are considered to be responsible for matrix (tissue) remodelling (Chuen et al, 2004). Tendon stem/ progenitor cells have been recently discovered and their capacity to differentiate into bone, cartilage or fat has been observed (Bi et al, 2007), as well as, the expression of certain stem cells markers (Oct4 and SSEA4 among others) (Lui and Chan, 2011;Zhang and Wang, 2010b). The percentage of tendon stem/ progenitor cells depends on age, species and type of tendon: younger specimens contain a higher percentage of tendon stem/progenitor cells (Zhou et al, 2010) and the functional fitness of the cells is higher when compared to aged specimens (Spindler et al, 1995).…”

“…Immediately after injury, a mix of cytokines and growth factors is released from the platelets and inflammatory cells,-such as macrophages, monocytes and neutrophils, attracted to the wound site ( Fig. 2) and produce tumour necrosis factor (TNF) or growth factors involved in neovascularisation, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and PDGF (Chazaud, 2014;Lynch et al, 1987). During healing, fibrin clot formation serves as a provisional scaffold, releasing a variety of growth factors, aiding the healing process.…”

“…The tissue repair mechanisms induced upon PDGF-BB delivery are carried through its generic chemotactic, mitogenic and angiogenic properties, as well as its synergistic actions with other growth factors Lynch et al, 1987;. PDGF has chemotactic and mitogenic effects on neutrophils, macrophages and phagocytes, responsible for breakdown and cleaning of tissue debris, as well as on tenocytes that enter the wound site to regenerate the damaged tissue.…”

“…Heparin is a highly sulphated glycosaminoglycan, possessing moderate or strong binding affinity for several growth factors, including PDGF, FGF, TGFβ and VEGF (Guan et al, 2004;Lyon et al, 1997;Mangrulkar et al, 1995). Investigated primarily with a focus to reduce thrombogenicity of materials in contact with blood, its use also spread to the development of drug delivery constructs.…”