Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68⁺/FXIII-A^- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α⁺ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

中文翻译：

---

来自前病态肥胖个体的脂肪组织来源的间充质基质细胞在体外指导巨噬细胞形成 M2 样特征。

肥胖在全球范围内持续增加，已被证明会不可逆转地损害脂肪组织间充质基质细胞 (ADSC) 的分化潜力和血管生成特性。由于这些细胞旨在用于再生医学，特别是用于治疗炎症性疾病，并且肥胖对 ADSC 的免疫调节特性的影响尚不清楚，因此我们在此研究了从以前的肥胖受试者（Ex-Ob）中分离出的 ADSC 将如何影响巨噬细胞分化和极化，因为这些细胞是炎症反应的主要指导者。对超重 (OW) 和 Ex-Ob 受试者的皮下脂肪组织 (SAT) 的分析表明，Ex-Ob SAT 中的巨噬细胞数量大约是其两倍，这些巨噬细胞包含在 CD68 ⁺ /FXIII-A ^-炎症库中。尽管如此，体外共培养实验表明，Ex-Ob ADSC 指示单核细胞分化为 M2 样形态，并且在 LPS 治疗诱导的炎症条件下，通过静息 M0 巨噬细胞抑制 HLA-DR 上调，产生类似百分比的 TNF-α。 α ⁺细胞，并抑制 IL-10 分泌，类似于用于比较的 OW-ADSC 和 BMSC，因为这些是可用于治疗目的的主要替代细胞类型。我们的结果表明，Ex-Ob ADSC 在巨噬细胞教育中反映了 OW-ADSC，有利于 M2 免疫表型和混合 (M1/M2) 分泌反应。这些结果具有转化潜力，因为它们提供了证据表明来自 Ex-Ob 和 OW 受试者的 ADSC 可用于符合条件的再生医学疗法。进一步的体内研究对于验证这些观察结果至关重要。