Biology of Tendon Stem Cells and Tendon in Aging

Lui, Pauline Po Yee; Wong, Chi Ming

doi:10.3389/fgene.2019.01338

Cited by 47 publications

(59 citation statements)

References 131 publications

(231 reference statements)

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“…with IL-1β, has been shown to increase tenocyte migration and proliferation, the capacity for which decreases with age. 80,83,87,88,[100][101][102][103][104][105][106] In this study, we observed a decrease in tenocyte migration and proliferation following inflammatory stimulation in all species (statistically significant for sheep tenocyte proliferation as well as rat and mouse tendon cell migration under constant inflammation) except rats (non-significant trend toward increased proliferation), which may be due to our use of tenocytes from individuals in diseaserelevant age groups. The overall gene expression of human tenocytes was most similar to murine under healthy, equine under transient and ovine under constant inflammatory conditions.…”

Section: Discussionmentioning

confidence: 61%

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research

Oreff

Fenu

Vogl

et al. 2021

Preprint

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For research on tendon injury, many different animal models are utilized; however, the extent to which these species simulate the clinical condition and disease pathophysiology has not yet been critically evaluated. Considering the importance of inflammation in tendon disease, this study compared the cellular and molecular features of inflammation in tenocytes of humans and four common model species (mouse, rat, sheep, and horse). While mouse and rat tenocytes most closely equalled human tenocytes low proliferation capacity and the negligible effect of inflammation on proliferation, the wound closure speed of humans was best approximated by rats and horses. The overall gene expression of human tenocytes was most similar to mice under healthy, to horses under transient and to sheep under constant inflammatory conditions. Humans were best matched by mice and horses in their tendon marker and collagen expression, by horses in extracellular matrix remodelling genes, and by rats in inflammatory mediators. As no single animal model perfectly replicates the clinical condition and sufficiently emulates human tenocytes, fit-for-purpose selection of the model species for each specific research question and combination of data from multiple species will be essential to optimize translational predictive validity.

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Section: Discussionmentioning

confidence: 61%

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research

Oreff

Fenu

Vogl

et al. 2021

Preprint

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“…However, due to the limited availability of these cells, they must be culture expanded. Unfortunately, in vitro expansion has been reported to cause the cells to lose their phenotypic markers [189] and studies have demonstrated that the number of TDSCs are greatly reduced with aging, showing diminished proliferative capacity [190,191]. With this in mind, other cell sources are being investigated for therapeutic use.…”

Section: Stimulating Tendon and Ligament Repairmentioning

confidence: 99%

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

Desai

Jayasuriya

2020

Bioengineering

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Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues. As expected, each of the two strategies have their own advantages and limitations (which we describe), especially when considering the diverse microenvironments of different skeletal tissues like bone, tendon/ligament, and cartilage/fibrocartilage. This paper also discusses stem/progenitor cells commonly used for repairing different skeletal tissues, and it lists ongoing clinical trials that have risen from the implementation of these cells and strategies. Lastly, we discuss our own thoughts on where the field is headed in the near future.

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“…Moreover, it has been reported that the regenerative capacity of aged cells can be restored when exposed to a young environment. These findings suggest opportunities to reverse the aging process of tissues by targeting their niche (Lui and Wong, 2020). As such, MSC-based strategies isolated from neonatal sources might represent promising therapeutic tools for tendon repair and regeneration (Sevivas et al, 2018).…”

Section: Introductionmentioning

confidence: 97%

The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research

Meeremans

Walle

Vlierberghe

et al. 2021

Front. Cell Dev. Biol.

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Overuse tendon injuries are a major cause of musculoskeletal morbidity in both human and equine athletes, due to the cumulative degenerative damage. These injuries present significant challenges as the healing process often results in the formation of inferior scar tissue. The poor success with conventional therapy supports the need to search for novel treatments to restore functionality and regenerate tissue as close to native tendon as possible. Mesenchymal stem cell (MSC)-based strategies represent promising therapeutic tools for tendon repair in both human and veterinary medicine. The translation of tissue engineering strategies from basic research findings, however, into clinical use has been hampered by the limited understanding of the multifaceted MSC mechanisms of action. In vitro models serve as important biological tools to study cell behavior, bypassing the confounding factors associated with in vivo experiments. Controllable and reproducible in vitro conditions should be provided to study the MSC healing mechanisms in tendon injuries. Unfortunately, no physiologically representative tendinopathy models exist to date. A major shortcoming of most currently available in vitro tendon models is the lack of extracellular tendon matrix and vascular supply. These models often make use of synthetic biomaterials, which do not reflect the natural tendon composition. Alternatively, decellularized tendon has been applied, but it is challenging to obtain reproducible results due to its variable composition, less efficient cell seeding approaches and lack of cell encapsulation and vascularization. The current review will overview pros and cons associated with the use of different biomaterials and technologies enabling scaffold production. In addition, the characteristics of the ideal, state-of-the-art tendinopathy model will be discussed. Briefly, a representative in vitro tendinopathy model should be vascularized and mimic the hierarchical structure of the tendon matrix with elongated cells being organized in a parallel fashion and subjected to uniaxial stretching. Incorporation of mechanical stimulation, preferably uniaxial stretching may be a key element in order to obtain appropriate matrix alignment and create a pathophysiological model. Together, a thorough discussion on the current status and future directions for tendon models will enhance fundamental MSC research, accelerating translation of MSC therapies for tendon injuries from bench to bedside.

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Biology of Tendon Stem Cells and Tendon in Aging

Cited by 47 publications

References 131 publications

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair

The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research

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