Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression.

Abstract

Many studies of osteoarthritis (OA) have focused on the use of pain-suppressing drugs and stem cell treatments for cartilage repair. In a previous study, we reported the therapeutic effect of soluble C-C chemokine receptor type 2 (sCCR2) gene therapy on OA. Here, we aimed to demonstrate that sCCR2-expressing stem cells exhibits superior efficacy compared to mesenchymal stem cell (MSC) alone. We used monosodium iodoacetate to induce OA in a Wistar rat model for our experiments. Soluble form of CCR2 was transfected into chondrocytes. We analyzed both in vitro and in vivo systems using sCCR2 E3-transfected MSCs (sCEMs). MCP-1 reduced chondrogenesis, whereas sCEMs improved it. Additionally, disease development was suppressed in MCP-1 conditional knockout mice. In the OA rat model, injection of sCEMs showed significant effects with respect to pain control and reduction of joint cartilage inflammation and damage compared with injection of MOCK-MSCs. These findings indicate that sCEMs inhibit MCP-1, reducing pain and OA-induced cartilage damage and inducing chondroprotection. Inhibiting MCP-1/CCR2 signaling has a significant therapeutic effect on OA. Therefore, sCEM may be an effective treatment for OA.