The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases
The Phenotype and Secretory Activity of Adipose-Derived Mesenchymal Stem Cells (ASCs) of Patients with Rheumatic Diseases
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DOI：
10.3390/cells8121659
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发表时间：
2019-12-01
期刊：
影响因子：
6
通讯作者：
Kontny, Ewa
中科院分区：
文献类型：
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作者：
Kuca-Warnawin, Ewa;Skalska, Urszula;Kontny, Ewa
间充质干细胞(MSCs)具有免疫抑制和再生特性。脂肪组织是MSCs的替代来源，被称为脂肪来源的间充质干细胞(ASCs)。由于风湿性疾病(RD)中ASCs的生物学特性知之甚少，我们对RD/ASCs进行了基本的描述。用流式细胞术分析了健康供者(HD)、ASC株(n=5)及系统性红斑狼疮(SLE)、系统性硬化症(SSC)和强直性脊柱炎(AS)患者ASCs的细胞间黏附分子(ICAM)-1和血管细胞黏附分子(VCAM)-1的表型和表达。用酶联免疫吸附试验检测未经处理和细胞因子处理的ASCs分泌免疫调节因子的情况。RD/ASCs可降低CD90和ICAM-1的基础表达水平，并分别与IL-6和转化生长因子-β1的释放相关。与HD/ASCs相比，未处理和肿瘤坏死因子+干扰素-γ(TI)处理的RD/ASCs产生的前列腺素E_2(PGE(2))、IL-6、白血病抑制因子(LIF)和转化生长因子-β1的量相似，而IL-1ra、可溶性人白细胞抗原G(sHLA-G)和肿瘤坏死因子诱导基因(TSG)-6的量较多，而犬尿氨酸和半乳糖凝集素-3的量较少。Galectin-3基础分泌量与患者血沉(ESR)值呈负相关。干扰素-α和IL-23分别略微增加SLE/ASCs和AS/ASCs Galectin-3的释放。转化生长因子-β1上调SSC/ASCs分泌PGE(2)。结论：RD/ASCs的基本特征是CD90和ICAM-1表达水平降低，IL-1ra、TSG-6和sHLA-G分泌上调，而犬尿氨酸和半乳糖凝集素-3的释放减少。这些异常可能改变了RD/ASCs的生物学活性。
Mesenchymal stem/stromal cells (MSCs) have immunosuppressive and regenerative properties. Adipose tissue is an alternative source of MSCs, named adipose-derived mesenchymal stem cells (ASCs). Because the biology of ASCs in rheumatic diseases (RD) is poorly understood, we performed a basic characterization of RD/ASCs. The phenotype and expression of adhesion molecules (intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1) on commercially available healthy donors (HD), ASC lines (n = 5) and on ASCs isolated from patients with systemic lupus erythematosus (SLE, n = 16), systemic sclerosis (SSc, n = 17) and ankylosing spondylitis (AS, n = 16) were analyzed by flow cytometry. The secretion of immunomodulatory factors by untreated and cytokine-treated ASCs was measured by ELISA. RD/ASCs have reduced basal levels of CD90 and ICAM-1 expression, correlated with interleukin (IL)-6 and transforming growth factor (TGF)-beta 1 release, respectively. Compared with HD/ASCs, untreated and tumour necrosis factor (TNF) + interferon (IFN)-gamma (TI)-treated RD/ASCs produced similar amounts of prostaglandin E2 (PGE(2)), IL-6, leukemia inhibiting factor (LIF), and TGF-beta 1, more IL-1Ra, soluble human leukocyte antigen G (sHLA-G) and tumor necrosis factor-inducible gene (TSG)-6, but less kynurenines and galectin-3. Basal secretion of galectin-3 was inversely correlated with the patient's erythrocyte sedimentation rate (ESR) value. IFN-alpha and IL-23 slightly raised galectin-3 release from SLE/ASCs and AS/ASCs, respectively. TGF-beta 1 up-regulated PGE(2) secretion by SSc/ASCs. In conclusion, RD/ASCs are characterized by low basal levels of CD90 and ICAM-1 expression, upregulated secretion of IL-1Ra, TSG-6 and sHLA-G, but impaired release of kynurenines and galectin-3. These abnormalities may modify biological activities of RD/ASCs.