Reparative tendon regeneration influenced by multipotent mesenchymal stromal cell secretome: experimental study
Authors:   K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Kachalin M.D. , Borkhunova E.N. ,   K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Pozyabin S.V. ,   K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Mikhaleva L.M. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Centre of Surgery, Moscow, Areshidze D.A. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Centre of Surgery, Moscow, Kozlova M.A. ,   Avtsyn Research Institute of Human Morphology of FSBSI Petrovsky National Research Centre of Surgery, Moscow, Dovgii A.I. ,   T-Helper Cell Technologies, LLC, Moscow
Published: June 2023

Introduction. Improving treatments for tendon injuries remains a topical issue in biology and medicine. Tendon structure is predisposed to scar formation, with significant regions of dystrophy leading to chronic and recurrent tendinitis. Stem cell regenerative therapy including mesenchymal stromal cell secretome is among promising treatments to improve patient outcomes. Standardized cytokine concentrations can be incorporated into the secretome, which may include both pro- and anti-inflammatory cytokines. This article addresses the use of stromal cell secretome for tendon injury regeneration, which is poorly studied. Materials and methods. The study included 95 white outbred rats (males, weight 120 g), which were divided into three groups: Group I comparison (n=35), Group II experimental (n=35), and Group III control (n=25). Animals in Groups I and II were anesthetized with isoflurane and their calcaneal tendons were dissected and sutured. Animals in Group I were treated with saline solution, whereas Group II received stromal cell secretome. The wounds were subsequently sutured. One week after the manipulation, the animals received the second treatment around the tendon. The animals were withdrawn from the experiment on days 1, 7, 14, and 60. We analyzed the samples using light microscopy with morphometry and transmission electron microscopy. Results. Treating tendons with stromal cell secretome (Group II) is accompanied by less pronounced inflammation and shows no dystrophic changes. The collagen bundles in the regenerate are parallel to each other, with vasculature being normalized and the number of fibroblasts having a slight increase. The control samples, however, showed inflammation, dystrophy, and scarring with hypovascularization of the regenerate. Moreover, the total fibroblast count in the tissue of the control samples elevated significantly. The regenerate in Group II was slightly thicker than in Group III, while in Group I, the regenerate was thinner than in Group III. Conclusion. Mesenchymal stromal cell secretome greatly contributes to tendon healing. Microscopic tendon regenerate structure is similar to that of the intact sample, suggesting its functional recovery. Keywords: multipotent mesenchymal stromal cells, secretome, cytokines, tendon, trauma, reparative regeneration