Mesenchymal Stromal Cells Adapt to Chronic Tendon Disease Environment with an Initial Reduction in Matrix Remodeling

Carla U Doll,Janina Burk,Sabine Niebert

doi:10.3390/ijms222312798

Carla U Doll, Janina Burk + Show 1 more

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https://doi.org/10.3390/ijms222312798

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Abstract

Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix. Equine MSCs were cultured either as cell aggregates or on scaffolds from healthy or diseased equine tendons. Higher expression of tendon-related matrix genes and tissue inhibitors of metalloproteinases (TIMPs) was found in aggregate cultures. However, the tenogenic transcription factor scleraxis was upregulated on healthy and diseased tendon scaffolds. Matrix metalloproteinase (MMPs) expression and activity were highest in healthy scaffold cultures but showed a strong transient decrease in diseased scaffold cultures. The release of glycosaminoglycan and collagen was also higher in scaffold cultures, even more so in those with tendon disease. This study points to an early suppression of MSC matrix remodeling activity by diseased tendon matrix, while tenogenic differentiation remained unaffected.

Highlights

Tendon disease is a common reason for early retirement from athletic activities, as their incidence increases with age and exercise level [1,2]
The tenogenic transcription factor scleraxis was upregulated in the mesenchymal stromal cell (MSC) in healthy tendon scaffold cultures as compared to aggregate cultures (p < 0.05 at day 6)
MSCs from one representative donor horse, as chosen based on the results described above, were cultured either on decellularized healthy tendon scaffolds or on decellularized tendon scaffolds with chronic disease from n = 5 donor horses per group for 3, 6, or 21 days

Summary

Introduction

Tendon disease is a common reason for early retirement from athletic activities, as their incidence increases with age and exercise level [1,2]. Once an acute tendon injury has occurred, the healing process begins with a short inflammatory phase of a few days up to 2 weeks Even during this early phase and continuing successively, connective tissue is formed under vascular sprouting and cellular infiltration, showing increased levels of type III collagen and altered concentrations of glycosaminoglycans. The composition and fiber organization within the tendon remain altered, and the newly formed scar tissue can achieve the strength but not the elasticity of healthy tendon tissue. This often leads to re-injuries, and chronic disease progresses when training is resumed [3]

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