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Background <p>Inflammatory pain is a hallmark symptom of osteoarthritis (OA), characterized by spontaneous hypersensitivity resulting from tissue damage and chronic inflammation. This study investigates the pain-relieving and cartilage-protective potential of extracellular vesicles (EVs) derived from human adipose-derived stem cells (hASCs) as a cell-free therapeutic approach for OA.</p> Methods <p>hASC-EVs were isolated via multi-filtrations based on tangential flow filtration (TFF) and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), zeta potential measurement, flow cytometry and Liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomic analysis. An in vitro inflammatory OA model was established by treating human osteoarthritic chondrocytes (HC-OA) with interleukin-1β (IL-1β). The expression of inflammation- and pain-related genes was assessed by quantitative PCR (qPCR), and modulation of the Phosphoinositide 3-kinase / Protein kinase B (PI3K/Akt) signaling pathway was analyzed using an antibody array. In vivo therapeutic effects were evaluated in seven-week-old male Wistar rats using a monosodium iodoacetate (MIA)-induced OA model following intra-articular injection of hASC-EVs. Pain behavior was assessed via paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and weight-bearing tests. Cartilage protection was evaluated by histological and immunohistochemical stainings (IHC).</p> Results <p>hASC-EVs were efficiently internalized into chondrocytes and significantly suppressed IL-1β-induced expression of pain and inflammatory markers (<i>TRPA1</i>,<i> COX-2</i>,<i> MMP-2</i>,<i> MMP-3</i>,<i> and MMP-9</i>). Additionally, hASC-EVs down-regulated key PI3K/Akt signaling genes, such as <i>PIK3CA</i> and <i>AKT1</i>. In vivo, hASC-EV treatment markedly improved PWL, PWT, and weight-bearing performance compared with untreated OA rats. Histological and immunohistochemical analyses revealed reduction of inflammatory cytokine expression and preservation of collagen type II, indicating both anti-inflammatory and cartilage-protective effects.</p> Conclusions <p>hASC-EVs exhibited robust pain-relieving and cartilage-preserving effects in an OA rat model, highlighting their potential as a promising cell-free therapeutic strategy for the management of OA-related pain and joint degeneration.</p> Graphical Abstract <p></p>

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Extracellular vesicles from human adipose-derived stem cells relieve pain and inflammation in a rat model of knee osteoarthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Woo Sung Kim,
  • Chang Hee Woo,
  • Kyoung Soo Lee,
  • Young Chan Choi,
  • Ye Eun Yun,
  • Ji Suk Choi,
  • Yong Woo Cho

摘要

Background

Inflammatory pain is a hallmark symptom of osteoarthritis (OA), characterized by spontaneous hypersensitivity resulting from tissue damage and chronic inflammation. This study investigates the pain-relieving and cartilage-protective potential of extracellular vesicles (EVs) derived from human adipose-derived stem cells (hASCs) as a cell-free therapeutic approach for OA.

Methods

hASC-EVs were isolated via multi-filtrations based on tangential flow filtration (TFF) and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), zeta potential measurement, flow cytometry and Liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomic analysis. An in vitro inflammatory OA model was established by treating human osteoarthritic chondrocytes (HC-OA) with interleukin-1β (IL-1β). The expression of inflammation- and pain-related genes was assessed by quantitative PCR (qPCR), and modulation of the Phosphoinositide 3-kinase / Protein kinase B (PI3K/Akt) signaling pathway was analyzed using an antibody array. In vivo therapeutic effects were evaluated in seven-week-old male Wistar rats using a monosodium iodoacetate (MIA)-induced OA model following intra-articular injection of hASC-EVs. Pain behavior was assessed via paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and weight-bearing tests. Cartilage protection was evaluated by histological and immunohistochemical stainings (IHC).

Results

hASC-EVs were efficiently internalized into chondrocytes and significantly suppressed IL-1β-induced expression of pain and inflammatory markers (TRPA1, COX-2, MMP-2, MMP-3, and MMP-9). Additionally, hASC-EVs down-regulated key PI3K/Akt signaling genes, such as PIK3CA and AKT1. In vivo, hASC-EV treatment markedly improved PWL, PWT, and weight-bearing performance compared with untreated OA rats. Histological and immunohistochemical analyses revealed reduction of inflammatory cytokine expression and preservation of collagen type II, indicating both anti-inflammatory and cartilage-protective effects.

Conclusions

hASC-EVs exhibited robust pain-relieving and cartilage-preserving effects in an OA rat model, highlighting their potential as a promising cell-free therapeutic strategy for the management of OA-related pain and joint degeneration.

Graphical Abstract