CD146+ bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) play key roles in the perivascular niche, skeletogenesis, and hematopoietic support; however, comprehensive evaluation of therapeutic potency has yet to be determined. In this study, in vitro inflammatory priming to crude human BM‐MSCs (n = 8) captured a baseline of signature responses, including enriched CD146+ with coexpression of CD107aHigh, CXCR4High, and LepRHigh, transcriptional profile, enhanced secretory capacity, and robust immunomodulatory secretome and function, including immunopotency assays (IPAs) with stimulated immune cells. These signatures were significantly more pronounced in CD146+ (POS)‐sorted subpopulation than in the CD146− (NEG). Mechanistically, POS BM‐MSCs showed a markedly higher secretory capacity with significantly greater immunomodulatory and anti‐inflammatory protein production upon inflammatory priming compared with the NEG BM‐MSCs. Moreover, IPAs with stimulated peripheral blood mononuclear cells and T lymphocytes demonstrated robust immunosuppression mediated by POS BM‐MSC while inducing significant frequencies of regulatory T cells. in vivo evidence showed that POS BM‐MSC treatment promoted pronounced M1‐to‐M2 macrophage polarization, ameliorating inflammation/fibrosis of knee synovium and fat pad, unlike treatment with NEG BM‐MSCs. These data correlate the expression of CD146 with innately higher immunomodulatory and secretory capacity, and thus therapeutic potency. This high‐content, reproducible evidence suggests that the CD146+ (POS) MSC subpopulation are the mediators of the beneficial effects achieved using crude BM‐MSCs, leading to translational implications for improving cell therapy and manufacturing.

中文翻译：

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CD146+ 间充质干细胞/基质细胞的特征质量属性与高治疗和分泌效力相关

CD146+ 骨髓间充质干/基质细胞 (BM-MSCs) 在血管周围生态位、骨骼生成和造血支持中发挥关键作用；然而，尚未确定对治疗效力的综合评价。在这项研究中，对原始人 BM-MSC（n = 8）的体外炎症引发捕获了特征反应的基线，包括富集的 CD146+ 与 CD107aHigh、CXCR4High 和 LepRHigh 的共表达、转录谱、增强的分泌能力和强大的免疫调节分泌组和功能，包括使用受刺激的免疫细胞进行免疫效力测定 (IPA)。这些特征在 CD146+ (POS) 排序的亚群中比在 CD146- (NEG) 中更明显。从机制上讲，与 NEG BM-MSCs 相比，POS BM-MSCs 显示出显着更高的分泌能力，炎症引发后免疫调节和抗炎蛋白的产生显着增加。此外，具有受刺激的外周血单核细胞和 T 淋巴细胞的 IPA 表现出由 POS BM-MSC 介导的强大免疫抑制，同时诱导显着频率的调节性 T 细胞。体内证据表明，与 NEG BM-MSC 治疗不同，POS BM-MSC 治疗促进了显着的 M1 到 M2 巨噬细胞极化，改善了膝关节滑膜和脂肪垫的炎症/纤维化。这些数据将 CD146 的表达与先天较高的免疫调节和分泌能力相关联，从而具有治疗效力。这种高内涵，