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间充质干细胞的免疫抑制机制通过贫血小板血浆和胎牛血清补充培养基的差异调节。

The immunosuppressive mechanisms of mesenchymal stem cells are differentially regulated by platelet poor plasma and fetal bovine serum supplemented media.

机构信息

Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, DF, Brazil; Laboratório de Hematologia, Departamento de Farmácia, Universidade de Brasília, Brasília, DF, Brazil.

Laboratório de Farmacologia Molecular, Departamento de Farmácia, Universidade de Brasília, Brasília, DF, Brazil.

出版信息

Int Immunopharmacol. 2020 Feb;79:106172. doi: 10.1016/j.intimp.2019.106172. Epub 2020 Jan 8.

Abstract

PURPOSE

Mesenchymal Stem Cells (MSCs) can interact with and modulate the functions of all immune cells, suppressing both the innate and adaptive immune responses. Currently, most of the in vitro studies which have led to the description of MSC properties have resulted from MSC culture in the presence of fetal bovine serum (FBS), in spite of the recognition of FBS limitations and attempts to substitute this component from the MSC media.

METHODS

Herein, we compare FBS and Platelet Poor Plasma (PPP) as MSC media supplements, according to Adipose-derived MSC (AMSC) phenotype, proliferation and immunoregulatory mechanisms.

RESULTS

Interestingly, despite maintaining the classic phenotypic profile of MSCs, PPP cultured AMSCs showed impaired proliferative potential. Furthermore, our results clearly show that AMSC culture with PPP leads to decreased expression of soluble immunosuppressive factors, which resulted in decreased capacity of inducing regulatory T-cells (Tregs) generation by these cells. In contrast, PPP supplementation promoted enhanced VCAM-1 and ICAM-1 expression on AMSC surface. Therefore, AMSCs cultured with PPP showed limited potential to produce soluble immunomodulatory factors, indicating a reduced capacity to control the immune system thought paracrine activity.

CONCLUSION

Overall, our data sheds light on the importance of culture media supplementation for MSC immunomodulatory behavior, as well as serving as an alert regarding the complexity of replacing FBS in MSC culture.

摘要

目的

间充质干细胞(MSCs)可以与所有免疫细胞相互作用并调节其功能,抑制固有和适应性免疫反应。目前,大多数导致描述 MSC 特性的体外研究都是在胎牛血清(FBS)存在的情况下进行 MSC 培养的结果,尽管已经认识到 FBS 的局限性,并试图从 MSC 培养基中替代该成分。

方法

在此,我们根据脂肪来源的间充质干细胞(AMSC)表型、增殖和免疫调节机制,比较 FBS 和血小板贫血浆(PPP)作为 MSC 培养基的补充。

结果

有趣的是,尽管 PPP 培养的 AMSCs 保持了 MSC 的经典表型特征,但增殖潜力受损。此外,我们的结果清楚地表明,PPP 培养 AMSC 会导致可溶性免疫抑制因子的表达减少,从而降低这些细胞诱导调节性 T 细胞(Tregs)生成的能力。相比之下,PPP 补充剂促进了 AMSC 表面 VCAM-1 和 ICAM-1 的表达增加。因此,PPP 培养的 AMSCs 产生可溶性免疫调节因子的潜力有限,表明通过旁分泌活性控制免疫系统的能力降低。

结论

总的来说,我们的数据阐明了培养基补充对于 MSC 免疫调节行为的重要性,并提醒人们在 MSC 培养中替代 FBS 的复杂性。

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