Enhanced Effect of Tendon Stem/Progenitor Cells Combined With Tendon-Derived Decellularized Extracellular Matrix on Tendon Regeneration

Abstract

Decellularized extracellular matrices have been clinically used for tendon regeneration. However, only a few systematic studies have compared tendon stem/progenitor cells to mesenchymal stromal cells on the tendon-derived decellularized matrix. In the present study, we prepared extracellular matrix derived from porcine tendons and seeded with tendon stem/progenitor cells, embryonic stem cell-derived mesenchymal stromal cells or without stem cells. Then we implanted the mixture (composed of stem cells and scaffold) into the defect of a rat Achilles tendon. Next, 4 weeks post-surgery the regenerated tendon tissue was collected. Histological staining, immunohistochemistry, determination of collagen content, transmission electron microscopy, and biomechanical testing were performed to evaluate the tendon structure and biomechanical properties. Our study collectively demonstrated that decellularized extracellular matrix derived from porcine tendons significantly promoted the regeneration of injured tendons when combined with tendon stem/progenitor cells or embryonic stem cell-mesenchymal stromal cells. Compared to embryonic stem cell-mesenchymal stromal cells, tendon stem/progenitor cells combined with decellularized matrix showed more improvement in the structural and biomechanical properties of regenerated tendons in vivo. These findings suggest a promising strategy for functional tendon tissue regeneration and further studies are warranted to develop a functional tendon tissue regeneration utilizing tendon stem/progenitor cells integrated with a tendon-derived decellularized matrix.