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比较脂肪源性和骨髓源性干细胞在保护 M1 巨噬细胞源性泡沫细胞免受 ox-LDL 诱导的炎症中的作用。

Comparison of adipose‑ and bone marrow‑derived stem cells in protecting against ox‑LDL‑induced inflammation in M1‑macrophage‑derived foam cells.

机构信息

Division of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Key Laboratory of Education Ministry for Myocardial Ischemia, Harbin, Heilongjiang 150086, P.R. China.

Division of Thoracic Surgery, Tang Du Hospital of Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Mol Med Rep. 2019 Apr;19(4):2660-2670. doi: 10.3892/mmr.2019.9922. Epub 2019 Feb 1.

Abstract

Adipose‑derived stem cells (ADSCs) and bone marrow‑derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co‑cultured with M1 foam macrophages via treatment with oxidized low‑density lipoprotein (ox‑LDL) would lead to similar or improved anti‑inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox‑LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography‑quadrupole time‑of‑flight‑mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis‑9, trans‑11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox‑LDL. Overall, 2x106 ADSCs, BMSCs or BMSCs+cis‑9, trans‑11 were co‑cultured with M1 foam macrophages. Anti‑inflammatory capability, phagocytic activity, anti‑apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis‑9, trans‑11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs or BMSCs+cis‑9, trans‑11. Additionally, BMSCs+cis‑9, trans‑11 also demonstrated marked improvement in anti‑inflammatory capability, phagocytic activity, anti‑apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis‑9, trans‑11. This may be an important mechanism to regulate macrophage immune function.

摘要

脂肪来源的干细胞(ADSCs)和骨髓来源的干细胞(BMSCs)被认为是间充质基质细胞(MSCs)的潜在来源,可用于动脉粥样硬化的细胞治疗。本研究旨在探讨与 BMSCs 相比,经氧化低密度脂蛋白(ox-LDL)处理的与 M1 泡沫巨噬细胞共培养的 ADSCs 是否会产生类似或改善的抗炎作用。从 10 名冠心病(CHD)患者中分离 ADSCs、外周血单核细胞、BMSCs 和 ox-LDL。经过 3 次传代后,收集 ADSCs 和 BMSCs 的上清液,并通过液相色谱-四极杆飞行时间-质谱联用仪(6530;Agilent Technologies,Inc.,Santa Clara,CA,USA)进行系统分析。顺式-9,反式-11 被认为是 ADSCs 和 BMSCs 代谢特征差异的原因。这些外周血单核细胞通过流式细胞术进行鉴定。外周血单核细胞分化为 M1 巨噬细胞后,通过 ox-LDL 处理形成 M1 泡沫巨噬细胞。总体而言,将 2x106 ADSCs、BMSCs 或 BMSCs+cis-9,trans-11 与 M1 泡沫巨噬细胞共培养。比较这些组之间的抗炎能力、吞噬活性、抗凋亡能力和细胞活力。结果表明,ADSCs、BMSCs 或 BMSCs+cis-9,trans-11 处理泡沫细胞来源的 M1 巨噬细胞后,脂质滴的积累减少。一致地,ADSCs 表现出比 BMSCs 或 BMSCs+cis-9,trans-11 更好的抗炎能力、吞噬活性、抗凋亡能力和细胞活力。此外,与 BMSCs 相比,BMSCs+cis-9,trans-11 也在抗炎能力、吞噬活性、抗凋亡能力和细胞活力方面表现出显著改善。这些结果表明,与单独的 BMSCs 或 BMSCs+cis-9,trans-11 相比,ADSCs 更适合用于移植治疗动脉粥样硬化。这可能是调节巨噬细胞免疫功能的一个重要机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b56/6423631/28e53bdfd198/MMR-19-04-2660-g00.jpg

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