Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons

Shih-Heng Chen,Ya-Hsuan Lin,Pang-Yun Chou,Feng-Huei Lin,Shih-Hsien Chen,Huang-Kai Kao,Zhi-Yu Chen

doi:10.3390/ijms222212373

Abstract

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

Highlights

Tendons are connective tissues that connect muscles to bone and transmit force from muscle to skeleton, generate range of motion in joints, and maintain tension in positioning [1]
The control group had more neutrophil infiltration than the Extracellular vesicles (EVs)-treated group. These results indicate that adipose-derived stem cells (ADSCs)-EV injection promotes tendon regeneration and may reduce inflammation, which is beneficial for tendon repair in clinical scenarios
The results of this study showed that the ADSC-EVs treated group expressed relatively higher tenomodulin content, implying that ADSC-EVs have the ability to promote tenocyte proliferation and extracellular matrix (ECM) remodeling, which reflects the results of tenocyte proliferation after treatment with EVs in our in vitro study

Summary

Introduction

Tendons are connective tissues that connect muscles to bone and transmit force from muscle to skeleton, generate range of motion in joints, and maintain tension in positioning [1]. Tendon injury is a common trauma that may cause morbidities such as adhesion and reduced range of motion in joints because of its prolonged healing time. This results in limitations in working ability and compromised quality of life. The prolonged healing of tendons stems from its characteristics, including hypovascularity and low metabolic activity, which are designed for tolerance of hypoxia during continuous exercise [3]. The prolonged inflammatory phase of the healing process can induce fibroblast activity and result in excessive scar formation and subsequent tendon adhesion, which would compromise the functional outcome of tendon repair [4]. Promoting tendon healing and reducing downtime remains a major clinical challenge [5]

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