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人脐带间充质干细胞来源的外泌体与基质结合纳米囊泡在骨关节炎治疗中的治疗潜力。

The Therapeutic Potential of Exosomes vs. Matrix-Bound Nanovesicles from Human Umbilical Cord Mesenchymal Stromal Cells in Osteoarthritis Treatment.

机构信息

Institute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

Laboratory of Clinical Smart Nanotechnologies, Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia.

出版信息

Int J Mol Sci. 2024 Oct 28;25(21):11564. doi: 10.3390/ijms252111564.

DOI:10.3390/ijms252111564
PMID:39519121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11545893/
Abstract

Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV-exosomes and matrix-bound nanovesicles (MBV)-both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration.

摘要

骨关节炎（OA）是一种退行性关节疾病，治疗选择有限，其中炎症在疾病进展中起着关键作用。间充质基质细胞（MSC）衍生的细胞外囊泡（EV）已被证明具有治疗 OA 的潜力，可通过调节炎症和缓解关节退行性过程。本研究通过差速超速离心法评估了两种 EV-外泌体和基质结合纳米囊泡（MBV）-均源自人脐带 MSC（UC-MSC）对 OA 治疗的疗效。使用不同表型的人单核细胞衍生巨噬细胞（MDM）体外研究 EV 的抗炎特性，并在体内使用内侧半月板切除术诱导的大鼠膝骨关节炎（MMx）模型。研究发现，两种 EV 均降低了 MDM 中的促炎细胞因子 IL-6 和 TNF-α。然而，外泌体的效果更好，更有效地保留了透明软骨的细胞外基质（ECM），并减少了滑膜炎，而 MBV 则不然。此外，外泌体下调了巨噬细胞和滑膜成纤维细胞中的炎症标志物（TNF-α、iNOS），并增加了 Arg-1 的表达，表明其具有更强的抗炎作用。这些结果表明 UC-MSC 外泌体作为 OA 的一种有前途的治疗选择，具有调节炎症和促进关节组织再生的潜力。

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