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Soluble CCR2-Expressing Mesenchymal Stem Cells Inhibit Osteoarthritis Development and Progression
Hyun Sik Na1, Seon-Young Lee1, Dong Hwan Lee2
1Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
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.
Insights
Soluble C-C chemokine receptor type 2 (sCCR2)-expressing stem cells (sCEMs) offer superior osteoarthritis treatment by inhibiting MCP-1, reducing pain, and protecting cartilage. This gene therapy shows significant therapeutic potential for OA.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Orthopedics
Background:
- Osteoarthritis (OA) is a degenerative joint disease often treated with pain relievers or stem cells.
- Previous research indicated therapeutic effects of soluble C-C chemokine receptor type 2 (sCCR2) gene therapy for OA.
- Mesenchymal stem cells (MSCs) are explored for cartilage repair, but their efficacy can be enhanced.
Purpose of the Study:
- To evaluate if sCCR2-expressing MSCs (sCEMs) demonstrate superior efficacy over MSCs alone in an OA model.
- To investigate the therapeutic mechanisms of sCEMs in inhibiting OA progression.
- To assess the potential of sCEMs as an effective OA treatment.
Main Methods:
- An osteoarthritis (OA) rat model was established using monosodium iodoacetate induction.
- Soluble C-C chemokine receptor type 2 (sCCR2) was transfected into chondrocytes and MSCs to create sCEMs.
- In vitro and in vivo experiments were conducted, including analysis in MCP-1 conditional knockout mice.
Main Results:
- MCP-1 was found to inhibit chondrogenesis, while sCEMs demonstrated an improvement in chondrogenesis.
- sCEM treatment significantly suppressed OA disease development in the rat model.
- sCEM injections reduced pain, inflammation, and cartilage damage in OA rats compared to MOCK-MSCs.
Conclusions:
- sCEMs effectively inhibit MCP-1, leading to reduced pain and cartilage damage in OA.
- The findings suggest that sCEMs possess chondroprotective properties.
- Inhibiting MCP-1/CCR2 signaling presents a promising therapeutic strategy for osteoarthritis.
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