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间充质干细胞通过抑制 CD4+T 淋巴细胞逆转高脂饮食诱导的小鼠非酒精性脂肪性肝病。

Mesenchymal stem cells reverse high‑fat diet‑induced non‑alcoholic fatty liver disease through suppression of CD4+ T lymphocytes in mice.

机构信息

Modern College of Arts and Science and School of Life Science, Shanxi Normal University, Linfen, Shanxi 041004, P.R. China.

Clinical Laboratory, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, P.R. China.

出版信息

Mol Med Rep. 2018 Mar;17(3):3769-3774. doi: 10.3892/mmr.2017.8326. Epub 2017 Dec 20.

Abstract

Although the multipotency of mesenchymal stem cells (MSCs) makes them an attractive choice for clinical applications, immune modulation is an important factor affecting MSC transplantation. At present, the effect of treatment with MSCs on non‑alcoholic fatty liver disease (NAFLD) has received little attention. In the present study, a compact bone‑derived method was used to isolate mouse MSCs (mMSCs) and a high‑fat diet was used to establish a mouse model of NAFLD. Immunophenotypic features of mMSCs were analyzed using flow cytometry. Paraffin sections were stained with hematoxylin and eosin to assess inflammation and steatosis, and with picrosirius red to assess fibrosis. Spleen leukocytes were analyzed by flow cytometry. The results demonstrated that compact bone‑derived MSC transplantation decreased high‑fat diet‑induced weight gain, expansion of subcutaneous adipose tissue, steatosis, lobular inflammation and liver fibrogenesis. Flow cytometry analysis of spleen leukocytes demonstrated that compact bone‑derived MSC transplantation suppressed the proliferation of cluster of differentiation (CD) 4+ T lymphocytes in the spleen, which had been induced by the high‑fat diet. In conclusion, compact bone‑derived MSCs may exhibit clinical value in the treatment of NAFLD through their capacity to suppress the activation of CD4+ T cells.

摘要

虽然间充质干细胞(MSCs)的多能性使其成为临床应用的理想选择,但免疫调节是影响 MSC 移植的一个重要因素。目前,MSCs 治疗非酒精性脂肪性肝病(NAFLD)的效果受到的关注较少。在本研究中,采用紧凑骨源性方法分离小鼠 MSCs(mMSCs),并使用高脂肪饮食建立 NAFLD 小鼠模型。采用流式细胞术分析 mMSCs 的免疫表型特征。用苏木精和伊红染色的石蜡切片评估炎症和脂肪变性,用苦味酸天狼猩红染色评估纤维化。用流式细胞术分析脾白细胞。结果表明,紧凑骨源性 MSC 移植可降低高脂肪饮食诱导的体重增加、皮下脂肪组织扩张、脂肪变性、肝小叶炎症和肝纤维化。对脾白细胞的流式细胞术分析表明,紧凑骨源性 MSC 移植抑制了高脂肪饮食诱导的 CD4+T 淋巴细胞在脾脏中的增殖。综上所述,紧凑骨源性 MSC 可能通过抑制 CD4+T 细胞的激活,在治疗 NAFLD 方面具有临床价值。

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