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黄芪甲苷对寻常型银屑病患者脂肪间充质干细胞免疫调节功能的影响。

Effect of astragaloside IV on the immunoregulatory function of adipose-derived mesenchymal stem cells from patients with psoriasis vulgaris.

机构信息

Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.

2 Beijing Key Laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy (BZ0381)/Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China.

出版信息

J Tradit Chin Med. 2022 Aug;42(4):513-519. doi: 10.19852/j.cnki.jtcm.20220516.002.

Abstract

OBJECTIVE

To compare the phenotype and adipogenic and osteogenic differentiation capacities of adipose-derived mesenchymal stem cells (AMSCs) isolated from patients with psoriasis vulgaris and healthy donors, and to explore the effects of astragaloside IV, a Traditional Chinese Medicine, on the immunoregulatory function of AMSCs.

METHODS

AMSCs were isolated from human adipose tissue and cultured for three generations in vitro. Cell phenotype and cell cycle analysis were performed by flow cytometry. Adipogenic and osteogenic differentiation of AMSCs was examined by lipid (oil red O) and alkaline phosphatase staining, respectively. Expression of inflammatory mediators was examined by real-time quantitative polymerase chain reaction analysis, and proliferation was quantified using the cell counting kit-8 assay.

RESULTS

Expression of CD29, CD44, and CD73 was higher in AMSCs from healthy donors than psoriasis patients, while the reverse was true for expression of CD45, CD31, and HLA-DR. AMSCs from psoriasis patients had a greater ability to undergo adipogenic differentiation than cells from healthy donors, whereas there was no significant difference in osteogenic differentiation between AMSCs from the two sources. Compared with AMSCs from healthy donors, psoriasis patient-derived AMSCs expressed lower levels of the anti-inflammatory cytokines interleukin-10 and trans-forming growth factor-β (TGF-β) and the immune checkpoint ligand programmed cell death 1 ligand 1 (PD-L1) (P < 0.05) and higher levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Incubation of AMSCs from psoriasis patients with astragaloside IV had no significant effect on pro-liferation but increased the expression of TGF-β and PD-L1 and decreased the expression of IFN-γ and TNF-α.

CONCLUSION

AMSCs from patients with psoriasis vulgaris display abnormal proliferation and adipogenesis and an enhanced pro-inflammatory phenotype. These defects were normalized by treatment with astragaloside IV, suggesting that this Traditional Chinese Medicine may be useful for restoring the immunoregulatory function of AMSCs and immune homeostasis in patients with psoriasis vulgaris.

摘要

目的

比较寻常型银屑病患者和健康供者来源的脂肪间充质干细胞(ADSCs)的表型和向成脂、成骨分化能力,并探讨中药黄芪甲苷对 ADSCs 免疫调节功能的影响。

方法

从人脂肪组织中分离 ADSCs 并在体外培养三代。通过流式细胞术进行细胞表型和细胞周期分析。通过油红 O 和碱性磷酸酶染色分别检测 ADSCs 的成脂和成骨分化。通过实时定量聚合酶链反应分析检测炎症介质的表达,并使用细胞计数试剂盒-8 检测增殖。

结果

与健康供者来源的 ADSCs 相比,银屑病患者来源的 ADSCs 表达更高的 CD29、CD44 和 CD73,而 CD45、CD31 和 HLA-DR 的表达则相反。银屑病患者来源的 ADSCs 向成脂分化的能力大于健康供者来源的细胞,而两种来源的 ADSCs 向成骨分化的能力没有显著差异。与健康供者来源的 ADSCs 相比,银屑病患者来源的 ADSCs 表达较低水平的抗炎细胞因子白细胞介素 10 和转化生长因子-β(TGF-β)和免疫检查点配体程序性细胞死亡 1 配体 1(PD-L1)(P<0.05),以及较高水平的促炎细胞因子肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)。用黄芪甲苷孵育银屑病患者来源的 ADSCs 对增殖没有显著影响,但增加了 TGF-β 和 PD-L1 的表达,降低了 IFN-γ 和 TNF-α 的表达。

结论

寻常型银屑病患者来源的 ADSCs 表现出异常增殖和成脂分化以及增强的促炎表型。用黄芪甲苷治疗可使这些缺陷正常化,表明这种中药可能有助于恢复寻常型银屑病患者 ADSCs 的免疫调节功能和免疫平衡。

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