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猪脱细胞软骨基质(pCAM)对骨关节炎治疗的免疫调节作用

Immunomodulation Effects of Porcine Cartilage Acellularized Matrix (pCAM) for Osteoarthritis Treatment.

作者信息

Kim Ji Seob, Kwon Hyeon Jae, Hwang In Sun, Lee Young Hwa, Yoon Kyung-Noh, Yun Hee-Woong, Jang Jae-Hyeok, Kim Seo Jeong, Aiana Zhoodatova, Kim Seungwoo, Moon Minhee, Kim Bongki, Kim Byoung Ju, Cha Byung-Hyun

机构信息

Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon-si, 24341, Republic of Korea.

ATEMs, Research and Development Institute, Seoul, 05836, Republic of Korea.

出版信息

Tissue Eng Regen Med. 2025 Jun;22(4):453-467. doi: 10.1007/s13770-024-00687-5. Epub 2025 Jan 9.

Abstract

BACKGROUND

Pain reduction, immunomodulation, and cartilage repair are key therapeutic goals in osteoarthritis (OA) treatment. In this study, we evaluated the therapeutic effects of porcine cartilage acellularized matrix (pCAM) derived from naive tissue and compared it with the synthetic material polynucleotides (PN) for OA treatment.

METHODS

pCAM was produced from porcine cartilage through physicochemical processing. LC-MS protein profiling identified the key proteins. In vitro experiments involved treating human synovial cell with pCAM and PN to assess cell viability and reductions in pro-inflammatory cytokines (IL-1β and IL-6). In vivo studies utilized a rat DMM-induced OA model. Pain was evaluated in weight-bearing tests, and inflammation reduction was confirmed using specific macrophage markers of CD68, CD86, and CD163 in immunohistochemical staining of synovial tissue. Cartilage regeneration was evaluated by histopathological analyses.

RESULTS

The major protein components of pCAM include factors integral to cartilage and ECM integrity. They also contain proteins that help reduce inflammation. In vitro studies revealed a decrease in pro-inflammatory cytokines and survival of synovial cells were observed. In vivo treatment with pCAM resulted in a reduction of pain and inflammation, while promoting cartilage regeneration, thereby accelerating the healing process in OA.

CONCLUSION

Our findings suggest that pCAM may contribute to the treatment of OA by alleviating synovial inflammation and supporting cartilage regeneration, thereby addressing both the inflammatory and degenerative aspects of the disease.

摘要

背景

减轻疼痛、免疫调节和软骨修复是骨关节炎(OA)治疗的关键治疗目标。在本研究中,我们评估了源自天然组织的猪软骨脱细胞基质(pCAM)的治疗效果,并将其与用于OA治疗的合成材料多核苷酸(PN)进行了比较。

方法

通过物理化学处理从猪软骨中制备pCAM。液相色谱-质谱联用(LC-MS)蛋白质谱分析鉴定关键蛋白质。体外实验包括用pCAM和PN处理人滑膜细胞,以评估细胞活力以及促炎细胞因子(IL-1β和IL-6)的减少情况。体内研究使用大鼠前交叉韧带切断(DMM)诱导的OA模型。在负重试验中评估疼痛情况,并在滑膜组织的免疫组织化学染色中使用CD68、CD86和CD163的特异性巨噬细胞标志物来确认炎症减轻情况。通过组织病理学分析评估软骨再生情况。

结果

pCAM的主要蛋白质成分包括对软骨和细胞外基质(ECM)完整性至关重要的因子。它们还含有有助于减轻炎症的蛋白质。体外研究显示促炎细胞因子减少,并且观察到滑膜细胞存活。用pCAM进行体内治疗导致疼痛和炎症减轻,同时促进软骨再生,从而加速OA的愈合过程。

结论

我们的研究结果表明,pCAM可能通过减轻滑膜炎症和支持软骨再生来促进OA的治疗,从而解决该疾病的炎症和退行性方面的问题。

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