Mesenchymal Stem Cells Empowering Tendon Regenerative Therapies

Abstract

Tendon tissues have limited healing capacity. The incidence of tendon injuries and the unsatisfactory functional outcomes of tendon repair are driving the search for alternative therapeutic approaches envisioning tendon regeneration. Cellular therapies aim at delivering adequate, regeneration-competent cell types to the injured tendon and toward ultimately promoting its reconstruction and recovery of functionality. Mesenchymal stem cells (MSCs) either obtained from tendons or from non-tendon sources, like bone marrow (BM-MSCs) or adipose tissue (ASCs), have been receiving increasing attention over the years toward enhancing tendon healing. Evidences from in vitro and in vivo studies suggest MSCs can contribute to accelerate and improve the quality of tendon healing. Nonetheless, the exact mechanisms underlying these repair events are yet to be fully elucidated. This review provides an overview of the main challenges in the field of cell-based regenerative therapies, discussing the role of MSCs in boosting tendon regeneration, particularly through their capacity to enhance the tenogenic properties of tendon resident cells.

Aged Tendon Stem/Progenitor Cells Are Less Competent to Form 3D Tendon Organoids Due to Cell Autonomous and Matrix Production Deficits

“…Tendons are dense connective tissues, which are critical for the integrity and function of our musculoskeletal system (Schiele et al, 2013;Docheva et al, 2015;Costa-Almeida et al, 2019). Tendons are hierarchically organized and have an extracellular matrix (ECM) consisting mainly of collagen type I and a smaller portion of other collagens and proteoglycans (Yan et al, 2018).…”

Supporting Cell-Based Tendon Therapy: Effect of PDGF-BB and Ascorbic Acid on Rabbit Achilles Tenocytes In Vitro

“…Different cell-based therapies, including biological and decellularized tissues [1,2], cell-seeded grafts from natural and synthetic biomaterials [3,4] or stem cell-based approaches [5] have been explored for the treatment of tendinopathies and tendon injuries. Among them, there are several reports on the use of mesenchymal stem cells (MSCs) for tendon cell-based therapy [6,7], or as a cell source for tissue engineered grafts and constructs where tenogenic differentiation was studied [8,9]. On the other hand, there are fewer reports exploring tenocytes for cell-based therapy [1,10,11], which might be due to the scarcity of donor tendons or loss of phenotype during in vitro expansion [12].…”

Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

“…Multipotent Mesenchymal Stem Cells (MSCs) are described as a promising therapeutic tool to manage tendon conditions in clinical applications [14]. Both in vivo and in vitro studies evidenced that MSCs can contribute to accelerate and improve the quality of tendon healing [15,16]. The use of MSCs, in combination with specific growth factors (GFs) is proposed as an innovative treatment for tendon healing and regeneration [17,18].…”