Tendon stem/progenitor cell ageing: Modulation and rejuvenation

Abstract

Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.

In Vitro Innovation of Tendon Tissue Engineering Strategies

“…The incapacity of complete healing derives from the nature of tendon with its poor cellularity, limited vascularization, and low metabolism [ 3 , 4 ]. The cellular component of the tendon is very low, and with age, it tends to diminish and change in morphology, with loss of stemness markers [ 5 , 6 , 7 ]. As the tendon is a mechanosensitive tissue and extracellular matrix (ECM) remodeling is influenced by mechanical stimulation [ 8 , 9 ], prolonged rehabilitation is considered a valid alternative to surgery that offers great support and is more efficient than pharmacological therapy.…”

“…In fact, in adult life, tendon becomes a specialized tissue with few cells that reduce their communication and synthetic activity [ 7 ]. With aging, TSPCs lose their stem markers, and they undergo a series of changes that affect their healing ability [ 6 ].…”

Interaction between Stem Cells and the Microenvironment for Musculoskeletal Repair

“…The tendon is to transmit muscular forces to the bone, permitting joint motion and subsequent body movement [4]. It was thought that the tendon only consists of tenocytes; nevertheless, the recent studies demonstrated that human and mouse tendons contain stem cells, namely, tendon stem/progenitor cells (TSPCs) [5]. In the review contributed by Dr. Zhang and colleagues, the recent advances in the identification and characterization of TSPCs and their interactions with extracellular matrix and mechanical loading were summarized; meanwhile, the authors outlined the challenges in understanding TSPC biology and function in vivo due to the heterogeneity and lack of specific markers and suggested that the mechanobiology of TSPCs and its role in tendon development, growth, repair, and pathology need to be better clarified.…”

Higher BMP Expression in Tendon Stem/Progenitor Cells Contributes to the Increased Heterotopic Ossification in Achilles Tendon With Aging

“…These findings supported the important role of altered TSPCs fate in pathological changes of chronic tendinopathy. During the aging process, TSPCs experienced an evident decrease in self-renewal and colony-forming ability and altered multi-differentiation capacity ( Tan et al, 2012 ; Ruzzini et al, 2014 ; Dai et al, 2019 ; Li et al, 2019 ). TSPCs tended to differentiate into osteoblasts with over-passaging, which was a common cell senescence model in vitro ( Tan et al, 2012 ).…”

“… Ruzzini et al (2014) indicated that aged TSPCs expressed higher levels of chondrogenic-related gene expression. Although there is no definite conclusion of these variations, the potential roles of altered TSPC differentiation capacity for age-related pathological changes in tendon were speculated ( Dai et al, 2019 ; Li et al, 2019 ).…”