Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair

Abstract

Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture. Nowadays, the application of various stem cell sources, including mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), for tendon repair has shown great potential, because these cells can differentiate into a tendon lineage and promote functional tendon repair. However, the mechanism underlying tenogenic differentiation remains unclear. Moreover, no widely adopted protocol has been established for effective and reproducible tenogenic differentiation because of the lack of definitive biomarkers for identifying the tendon differentiation cascades. This work is aimed at reviewing the literature over the past decade and providing an overview of background information on the clinical relevance of tendons and the urgent need to improve tendon repair; the advantages and disadvantages of different stem cell types used for boosting tendon repair; and the unique advantages of reported strategies for tenogenic differentiation, including growth factors, gene modification, biomaterials, and mechanical stimulation.

Optimizing tendon repair and regeneration: how does the in vivo environment shape outcomes following rupture of a tendon such as the Achilles tendon?

“…Prior to the reports of good versus poor outcomes following natural healing of the AT, and continuing to today, many studies have attempted to improve healing using a variety of interventions without attempting to segregate naturally occurring good and poor healers. While not all of the interventions have assessed efficacy for AT healing, the interventions utilized include growth factors [reviewed in (El-Sherif et al, 2023;Lin et al, 2023;Miescher et al, 2023;Rieber et al, 2023;Wang and Li, 2023)], acupuncture (Stewman, 2023), platelet-rich plasma (PRP) and variations (Markazi et al, 2022;Everts et al, 2023), other cell therapies including mesenchymal stem cells (MSC) (Chamberlain et al, 2017;Alt et al, 2021;Zhang et al, 2021;Jiang L. et al, 2023;Yuan et al, 2023;Zulkifli et al, 2023), and extracellular vesicles (EV) derived from MSC and related stem cells (Lu et al, 2021;Lyu et al, 2022;Wang and Li, 2023;Xue et al, 2023;Zou et al, 2023) and other cellular preparations (Aydin et al, 2023). Use of glucocorticoid injections to ostensibly control inflammation to enhance tendon healing or improve the local injury environment was variable and dependent on a variety of factors (Dietrich-Zagonel et al, 2018;Dietrich-Zagonel et al, 2022), and was often detrimental to healing (Dean et al, 2014).…”

An overview of the material science and knowledge of nanomedicine, bioscaffolds, and tissue engineering for tendon restoration

“…New techniques depending on growth agents and stem cell transplantation have been developed to address these issues ( Makuku et al, 2022 ; Yuan et al, 2023 ). Various preclinical studies demonstrate the capacity of a number of development factors to enhance the regenerative reaction and reduce scar development ( Makuku et al, 2022 ; Yuan et al, 2023 ).…”

“…New techniques depending on growth agents and stem cell transplantation have been developed to address these issues ( Makuku et al, 2022 ; Yuan et al, 2023 ). Various preclinical studies demonstrate the capacity of a number of development factors to enhance the regenerative reaction and reduce scar development ( Makuku et al, 2022 ; Yuan et al, 2023 ). In addition to stem cell transplantation and growth factors, novel tendon injury investigations concentrate on the creation of nano-material scaffolds ( Zhu et al, 2022 ).…”