人胚胎干细胞衍生的间充质基质细胞可减少 B10.RIII 小鼠严重实验性自身免疫性葡萄膜炎的发生。
Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Decrease the Development of Severe Experimental Autoimmune Uveitis in B10.RIII Mice.
机构信息
a Department of Ophthalmology , Stein Eye Institute , Los Angeles , California , USA.
b Molecular Biology IDP , UCLA , Los Angeles , California , USA.
出版信息
Ocul Immunol Inflamm. 2018;26(8):1228-1236. doi: 10.1080/09273948.2017.1343356. Epub 2017 Sep 15.
PURPOSE
We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis.
METHODS
B10.RIII mice were immunized with an uveitogenic peptide, and intraperitoneal injections of 5 million hESC-MSCs per animal were given on the same day. Behavioral light sensitivity assays, histological evaluation, cytokine production, and regulatory T cells were analyzed at the peak of the disease.
RESULTS
Histological and behavioral evidence demonstrated that early systemic treatment with hESC-MSCs decreases the development of severe EAU in B10.RIII mice. hESC-MSCs suppress Th17 and upregulate Th1 and Th2 responses as well as IL-2 and GM-CSF in splenocytes from hESC-MSC-treated mice.
CONCLUSIONS
MSCs that originate from hESC decrease the development of severe EAU in B10.RIII mice, likely through systemic immune modulation. Further investigation is needed to determine any potential effect on active EAU.
目的
我们研究了外源性给予人胚胎干细胞来源的间充质基质细胞（hESC-MSCs）对 B10.RIII 小鼠实验性自身免疫性葡萄膜炎（EAU）的影响，B10.RIII 小鼠是一种严重葡萄膜炎的小鼠模型。
方法
B10.RIII 小鼠用葡萄膜抗原肽免疫，在同一天对每只动物进行 500 万个人胚胎干细胞来源的间充质基质细胞的腹腔注射。在疾病高峰期分析行为光敏感试验、组织学评估、细胞因子产生和调节性 T 细胞。
结果
组织学和行为学证据表明，早期系统给予 hESC-MSCs 可减少 B10.RIII 小鼠严重 EAU 的发生。hESC-MSCs 抑制 Th17 并上调 Th1 和 Th2 反应以及 hESC-MSC 治疗小鼠脾细胞中的 IL-2 和 GM-CSF。
结论
来源于 hESC 的 MSC 可减少 B10.RIII 小鼠严重 EAU 的发生，可能通过全身免疫调节。需要进一步研究以确定其对活动性 EAU 的任何潜在影响。
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