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来自同一供体的人骨髓和脂肪组织间充质基质细胞免疫调节能力的比较分析。

Comparative analysis of the immunomodulatory capacities of human bone marrow- and adipose tissue-derived mesenchymal stromal cells from the same donor.

作者信息

Valencia Jaris, Blanco Belén, Yáñez Rosa, Vázquez Miriam, Herrero Sánchez Carmen, Fernández-García María, Rodríguez Serrano Concepción, Pescador David, Blanco Juan F, Hernando-Rodríguez Miriam, Sánchez-Guijo Fermín, Lamana María Luisa, Segovia José Carlos, Vicente Ángeles, Del Cañizo Consuelo, Zapata Agustín G

机构信息

Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.

Department of Hematology, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.

出版信息

Cytotherapy. 2016 Oct;18(10):1297-311. doi: 10.1016/j.jcyt.2016.07.006.

Abstract

BACKGROUND AIMS

The immunomodulatory properties of mesenchymal stromal cells (MSCs), together with their tissue regenerative potential, make them interesting candidates for clinical application.

METHODS

In the current study, we analyzed the in vitro immunomodulatory effects of MSCs derived from bone marrow (BM-MSCs) and from adipose tissue (AT-MSCs) obtained from the same donor on both innate and acquired immunity cells. BM-MSCs and AT-MSCs were expanded to fourth or fifth passage and co-cultured with T cells, monocytes or natural killer (NK) cells isolated from human peripheral blood and stimulated in vitro. The possible differing impact of MSCs obtained from distinct sources on phenotype, cell proliferation and differentiation, cytokine production and function of these immune cells was comparatively analyzed.

RESULTS

BM-MSCs and AT-MSCs induced a similar decrease in NK-cell proliferation, cytokine secretion and expression of both activating receptors and cytotoxic molecules. However, only BM-MSCs significantly reduced NK-cell cytotoxic activity, although both MSC populations showed the same susceptibility to NK-cell-mediated lysis. AT-MSCs were more potent in inhibiting dendritic-cell (DC) differentiation than BM-MSC, but both MSC populations similarly reduced the ability of DCs to induce CD4(+) T-cell proliferation and cytokine production. BM-MSCs and AT-MSCs induced a similar decrease in T-cell proliferation and production of inflammatory cytokines after activation.

CONCLUSIONS

AT-MSCs and BM-MSCs from the same donor had similar immunomodulatory capacity on both innate and acquired immunity cells. Thus, other variables, such as accessibility of samples or the frequency of MSCs in the tissue should be considered to select the source of MSC for cell therapy.

摘要

背景与目的

间充质基质细胞(MSCs)的免疫调节特性及其组织再生潜能使其成为临床应用的潜在候选细胞。

方法

在本研究中,我们分析了来自同一供体的骨髓间充质干细胞(BM-MSCs)和脂肪组织间充质干细胞(AT-MSCs)对天然免疫细胞和获得性免疫细胞的体外免疫调节作用。将BM-MSCs和AT-MSCs扩增至第4或第5代,与从人外周血分离的T细胞、单核细胞或自然杀伤(NK)细胞共培养,并进行体外刺激。比较分析了不同来源的MSCs对这些免疫细胞的表型、细胞增殖与分化、细胞因子产生及功能的可能不同影响。

结果

BM-MSCs和AT-MSCs均可使NK细胞增殖、细胞因子分泌以及活化受体和细胞毒性分子的表达出现相似程度的下降。然而,只有BM-MSCs能显著降低NK细胞的细胞毒性活性,尽管两种MSCs群体对NK细胞介导的裂解具有相同的敏感性。AT-MSCs在抑制树突状细胞(DC)分化方面比BM-MSCs更有效,但两种MSCs群体对DC诱导CD4(+) T细胞增殖和细胞因子产生能力的降低作用相似。BM-MSCs和AT-MSCs在活化后均可使T细胞增殖及炎性细胞因子产生出现相似程度的下降。

结论

来自同一供体的AT-MSCs和BM-MSCs对天然免疫细胞和获得性免疫细胞具有相似的免疫调节能力。因此,在选择用于细胞治疗的MSCs来源时,应考虑其他变量,如样本的可获取性或组织中MSCs的频率。

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