Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.
Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.
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DOI：
10.3390/cells11010024
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发表时间：
2021-12-22
期刊：
影响因子：
6
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Romano M;Elgueta R;McCluskey D;Ortega-Prieto AM;Stolarczyk E;Dazzi F;Lucendo-Villarin B;Meseguer-Ripolles J;Williams J;Fanelli G;Hay DC;Watt FM;Lombardi G
再生医学旨在通过刺激内源性组织修复或移植自体或同种异体细胞来替换受损组织。由于多能干细胞能够产生特定细胞类型的无限数量的细胞，无论是胚胎来源的干细胞还是通过体细胞重新编程诱导的干细胞，在再生医学领域都具有相当大的治疗价值。然而，无论哪种细胞类型，宿主免疫反应都是成功的障碍。本研究旨在探讨人多能干细胞(PSC)来源的肝细胞样细胞(HLCs)的体外免疫学特性。这些细胞表达MHC I类分子，但缺乏MHC II类分子和共刺激分子，如CD80和CD86。经干扰素-γ刺激后，HLC上调CD40、PD-L1和MHC-I类分子的表达。当HLCs与同种异体T细胞共同培养时，不能诱导T细胞的增殖；当T细胞被αCD3/CD2 8小球刺激时，HLCs通过IDO 1和色氨酸剥夺抑制其增殖。这些结果表明，至少在体外，PSC来源的HLCs具有免疫调节功能。
Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immunoregulatory functions, at least in vitro.
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影响因子：
8.8
作者：
Cisneros，Trinidad;Dillard，Danielle W.;Martinez，Olivia M.
通讯作者：
Martinez，Olivia M.
影响因子：
5.9
作者：
Petrus-Reurer, Sandra;Winblad, Nerges;Lanner, Fredrik
通讯作者：
Lanner, Fredrik
DOI：
10.1002/stem.2509
发表时间：
2017-03
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Davies LC;Heldring N;Kadri N;Le Blanc K
通讯作者：
Le Blanc K
影响因子：
46.9
作者：
Gornalusse GG;Hirata RK;Funk SE;Riolobos L;Lopes VS;Manske G;Prunkard D;Colunga AG;Hanafi LA;Clegg DO;Turtle C;Russell DW
通讯作者：
Russell DW
DOI：
10.1016/j.omtm.2019.12.015
发表时间：
2020-03-13
影响因子：
4.7
作者：
Mehler, Vera J.;Burns, Chris J.;Moore, Melanie L.
通讯作者：
Moore, Melanie L.