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白蛋白磁球分选富集的 CD146阳性脂肪间充质干细胞亚群减轻膝骨关节炎疼痛并促进软骨修复。

CD146-positive adipose-derived stem cells subpopulation enriched by albumin magnetic sphere ameliorates knee osteoarthritis pain and promotes cartilage repair.

机构信息

Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.

出版信息

J Orthop Surg Res. 2023 Dec 15;18(1):969. doi: 10.1186/s13018-023-04434-9.

Abstract

BACKGROUND

The use of adipose stem cell (ADSCs) subpopulations in cartilage repair remains poorly characterized. In this study, we constructed an albumin magnetic sphere with specific targeting of CD146 (CD146-AMs) for sorting a subpopulation of CD146-positive ADSCs (CD146 + ADSCs) and explored the role of CD146 + ADSCs on joint pain and cartilage repair in rats with knee osteoarthritis (KOA).

METHODS

CD146-AMs were prepared and analyzed in materialistic characterization tests. Subpopulations of CD146 + ADSCs were sorted using CD146-AMs. Surface labeling, viability, and proliferation of a subpopulation of CD146 + ADSCs were evaluated in vitro. Molecular characterization of mRNA and protein expression profiles was analyzed by microarray. A rat KOA pain model was established by the iodoacetic acid method, and KOA pain and the promotion of cartilage repair were assessed after treatment with bilateral joint cavity injections of CD146 + ADSCs.

RESULTS

The CD146-AMs prepared in this study had an average particle size of 242.63 ± 6.74 nm, an average potential of 33.82 ± 3.53 mv, and high CD146 targeting and low cytotoxicity. The positive rate of enriched CD146 + ADSCs was 98.21% and showed a high level of stem cell marker expression and good cell viability. Gene and protein expression profiles showed that CD146 + ADSCs have different cellular functions, especially in regulating inflammation. In the KOA model, low, medium and high concentrations of CD146 + ADSCs were able to improve KOA pain and promote cartilage repair in a concentration-dependent trend.

CONCLUSIONS

The CD146-AMs prepared in this study were able to safely and efficiently sort out the CD146 + ADSCs subpopulation. The subpopulation of CD146 + ADSCs has a unique molecular profile that ameliorates KOA pain and repairs cartilage damage in rats, providing a new idea for KOA treatment.

摘要

背景

脂肪干细胞(ADSCs)亚群在软骨修复中的应用仍未得到充分描述。在这项研究中,我们构建了一种具有特定靶向 CD146 的白蛋白磁球(CD146-AMs),用于分选 CD146 阳性 ADSCs(CD146+ADSCs)亚群,并探讨了 CD146+ADSCs 在膝骨关节炎(KOA)大鼠关节痛和软骨修复中的作用。

方法

在物质特征测试中制备和分析 CD146-AMs。使用 CD146-AMs 分选 CD146+ADSCs 亚群。体外评估 CD146+ADSCs 亚群的表面标记、活力和增殖。通过微阵列分析 mRNA 和蛋白质表达谱的分子特征。采用碘乙酸法建立大鼠 KOA 疼痛模型,经双侧关节腔注射 CD146+ADSCs 治疗后评估 KOA 疼痛和促进软骨修复。

结果

本研究制备的 CD146-AMs 平均粒径为 242.63±6.74nm,平均电位为 33.82±3.53mv,具有高 CD146 靶向性和低细胞毒性。富集的 CD146+ADSCs 的阳性率为 98.21%,表现出高水平的干细胞标志物表达和良好的细胞活力。基因和蛋白质表达谱显示,CD146+ADSCs 具有不同的细胞功能,特别是在调节炎症方面。在 KOA 模型中,低、中、高浓度的 CD146+ADSCs 能够以浓度依赖的方式改善 KOA 疼痛并促进软骨修复。

结论

本研究制备的 CD146-AMs 能够安全有效地分选 CD146+ADSCs 亚群。CD146+ADSCs 亚群具有独特的分子特征,可改善大鼠 KOA 疼痛并修复软骨损伤,为 KOA 治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/990d/10724978/1af6b0a190f9/13018_2023_4434_Fig1_HTML.jpg

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