Early transplantation of human umbilical cord mesenchymal stem cells is more effective in treating Achilles tendinopathy in a rat model

Abstract Objective Tendinopathy often causes pain and dysfunction that are difficult to treat. Various studies have examined the use of mesenchymal stem cells in treating tendinopathy, but the therapeutic effects differ depending on the dose and stage of tendinopathy. This study aims to investigate the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (Huc-MSCs) in treating Achilles tendinopathy. Methods Tendinopathy was induced in SD rats by injecting 50 μL of collagenase I solutioninto the Achilles tendon. Tendinopathy was established after one week for early-stage models and after four weeks for advanced-stage models. The early tendinopathy models were randomly divided into the MSC-1 and control-1 groups, whereas the advanced tendinopathy models were randomly divided into the MSC-2 and control-2 groups. The rats were injected with 50 μL of Huc-MSCs solution or normal saline into the tendon twice. Achilles tendons were sampled at four weeks after treatment for related evaluation. Results H&E staining revealed lower histological scores in the MSC groups compared to the control groups, with the MSC-1 group scoring slightly lower than the MSC-2 group. Alizarin red staining showed lower heterotopic ossification in the MSC groups than in the control groups. RT-qPCR showed lower mRNA expression of TNF-α, IL-1β and MMP-3 in the MSC groups compared to the control groups. Immunohistochemical staining showed that early MSC delivery promoted collagen I and TIMP-3 synthesis and decreased MMP-3 expression. Transmission electron microscopy revealed larger collagen fiber diameter in the MSC groups, with the MSC-1 group yielding larger collagen fiber than the MSC-2 group. Biomechanical results showed higher failure load and stiffness in the MSC-1 group compared to the MSC-2 group. Conclusion Local injection of Huc-MSCs into the Achilles tendon restores normal collagen fiber arrangement, promotes matrix synthesis, reduces inflammation and improves biomechanical properties of the injured Achilles tendon. Results showed that early delivery is more effective than advanced delivery.