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人去分化脂肪细胞的免疫调节作用:与脂肪来源干细胞的比较。

Immunomodulatory effect of human dedifferentiated fat cells: comparison with adipose-derived stem cells.

作者信息

Lin Yan, Mu Dali

机构信息

Department of Aesthetic and Reconstructive Breast Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144 People's Republic of China.

出版信息

Cytotechnology. 2023 Jun;75(3):231-242. doi: 10.1007/s10616-023-00572-4. Epub 2023 Feb 24.

Abstract

Dedifferentiated fat cells (DFATs), which are originated by the dedifferentiation of adipocytes, display surface markers of mesenchymal stem cells and are able to differentiate into different cell types, thus, yielding a huge therapeutic potential in repairing damaged tissues and organs. The use of allogeneic stem cells from healthy donors constitutes the basis of a new strategy for cell therapy in the field of transplantation and the first requirement for allografts is determining their immunological properties. In this study, human DFATs and ADSCs were passaged as in vitro models to investigate their immunomodulatory effects. Phenotypic analysis of cell surface markers and three-line differentiation protocols were used to identify stem cells. The immunogenic phenotypes of DFATs and ADSCs were analyzed by flow cytometry and a mixed lymphocyte reaction was used to assess their immune function. The characteristics of stem cells were confirmed by phenotypic identification of cell surface markers and three-line differentiation. Flow cytometry analysis showed that P3 generation DFATs and ADSCs contained human leukocyte antigen (HLA) class I molecules, but did not express HLA class II molecules and costimulatory molecules CD40, CD80 and CD86. Moreover, allogeneic DFATs and ADSCs could not induce the proliferation of peripheral blood mononuclear cells (PBMCs). In addition, both populations were shown to inhibit the Concanavalin A-stimulated proliferation of PBMCs and act as third-party cells responsible for inhibiting the mixed lymphocyte response. DFATs have immunosuppressive properties similar to ADSCs. Based on this, allogeneic DFATs have potential applications in tissue repair or cell therapy.

摘要

去分化脂肪细胞(DFATs)由脂肪细胞去分化产生,具有间充质干细胞的表面标志物,能够分化为不同的细胞类型,因此在修复受损组织和器官方面具有巨大的治疗潜力。使用来自健康供体的同种异体干细胞构成了移植领域细胞治疗新策略的基础,而异体移植物的首要要求是确定其免疫特性。在本研究中,将人DFATs和脂肪间充质干细胞(ADSCs)进行传代培养作为体外模型,以研究它们的免疫调节作用。通过细胞表面标志物的表型分析和三系分化方案来鉴定干细胞。采用流式细胞术分析DFATs和ADSCs的免疫原性表型,并利用混合淋巴细胞反应评估它们的免疫功能。通过细胞表面标志物的表型鉴定和三系分化来确认干细胞的特征。流式细胞术分析表明,第3代DFATs和ADSCs含有人类白细胞抗原(HLA)I类分子,但不表达HLA II类分子以及共刺激分子CD40、CD80和CD86。此外,同种异体DFATs和ADSCs不能诱导外周血单个核细胞(PBMCs)的增殖。另外,这两种细胞群体均显示出抑制伴刀豆球蛋白A刺激的PBMCs增殖的作用,并作为负责抑制混合淋巴细胞反应的第三方细胞。DFATs具有与ADSCs相似的免疫抑制特性。基于此,同种异体DFATs在组织修复或细胞治疗中具有潜在的应用价值。

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