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Background <p>Mesenchymal stromal cells (MSCs) have been increasingly explored as a minimally invasive treatment for osteoarthritis (OA), primarily due to their anti-inflammatory, immunomodulatory, and analgesic properties. However, MSC populations are biologically heterogeneous, and optimal cell phenotypes for intra-articular therapy remain unclear. CD271 has been identified as a marker associated with MSC subpopulations with enhanced regenerative potential. The aim of this study is to evaluate whether intra-articular injection of phenotype-selected CD271-positive adipose-derived MSCs (AD-MSCs) provides additional structural benefits compared with unselected AD-MSCs in experimental OA.</p> Methods <p>OA was induced in athymic rats by intra-articular injection of monoiodoacetate. Human infrapatellar fat pad-derived AD-MSCs were isolated and separated into CD271-positive fractions using magnetic-activated cell sorting. One week after OA induction, animals received intra-articular injection of saline, plastic-adherent AD-MSCs (PA-AD-MSCs), or CD271-positive AD-MSCs. Cartilage degeneration was assessed macroscopically and histologically using the Histologic/Histochemical Grading System (HHGS). Pain-related neuropeptides in dorsal root ganglia were analyzed by immunohistochemistry, and synovial inflammatory cytokines were quantified by ELISA.</p> Results <p>Both MSC-treated groups showed significant attenuation of cartilage degeneration, reduced synovial TNF-α and IL-6 levels, and decreased expression of pain-related neuropeptides compared with controls. The CD271-positive AD-MSC group had significantly lower HHGS scores than the PA-AD-MSC group at day 14, whereas macroscopic cartilage scores, inflammatory cytokine levels, and pain-related neuropeptide expression were not significantly different between AD-MSC-treated groups.</p> Conclusions <p>Intra-articular administration of AD-MSCs suppresses inflammation, pain-related signaling, and cartilage damage in OA. Enrichment for CD271-positive cells was associated with a modest early histological advantage, while anti-inflammatory and analgesic effects were comparable between AD-MSC-treated groups.</p>

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Early histological advantage of CD271-positive adipose-derived mesenchymal stromal cells isolated from the infrapatellar fat pad in experimental knee osteoarthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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  • Takumi Sakamoto,
  • Nozomi Aoki,
  • Takumi Shiotani,
  • Makoto Kitade,
  • Takamasa Noguchi,
  • Syunsuke Saito,
  • Hideaki Nakajima

摘要

Background

Mesenchymal stromal cells (MSCs) have been increasingly explored as a minimally invasive treatment for osteoarthritis (OA), primarily due to their anti-inflammatory, immunomodulatory, and analgesic properties. However, MSC populations are biologically heterogeneous, and optimal cell phenotypes for intra-articular therapy remain unclear. CD271 has been identified as a marker associated with MSC subpopulations with enhanced regenerative potential. The aim of this study is to evaluate whether intra-articular injection of phenotype-selected CD271-positive adipose-derived MSCs (AD-MSCs) provides additional structural benefits compared with unselected AD-MSCs in experimental OA.

Methods

OA was induced in athymic rats by intra-articular injection of monoiodoacetate. Human infrapatellar fat pad-derived AD-MSCs were isolated and separated into CD271-positive fractions using magnetic-activated cell sorting. One week after OA induction, animals received intra-articular injection of saline, plastic-adherent AD-MSCs (PA-AD-MSCs), or CD271-positive AD-MSCs. Cartilage degeneration was assessed macroscopically and histologically using the Histologic/Histochemical Grading System (HHGS). Pain-related neuropeptides in dorsal root ganglia were analyzed by immunohistochemistry, and synovial inflammatory cytokines were quantified by ELISA.

Results

Both MSC-treated groups showed significant attenuation of cartilage degeneration, reduced synovial TNF-α and IL-6 levels, and decreased expression of pain-related neuropeptides compared with controls. The CD271-positive AD-MSC group had significantly lower HHGS scores than the PA-AD-MSC group at day 14, whereas macroscopic cartilage scores, inflammatory cytokine levels, and pain-related neuropeptide expression were not significantly different between AD-MSC-treated groups.

Conclusions

Intra-articular administration of AD-MSCs suppresses inflammation, pain-related signaling, and cartilage damage in OA. Enrichment for CD271-positive cells was associated with a modest early histological advantage, while anti-inflammatory and analgesic effects were comparable between AD-MSC-treated groups.