Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Cytotherapy. 2012 Mar;14(3):274-84. doi: 10.3109/14653249.2011.635853. Epub 2011 Dec 5.
Human embryonic stem cell (hESC)-derived mesenchymal stromal cells (MSC) (hESC-MSC) are an alternative source of MSC to bone marrow (BM)-derived MSC (BM-MSC), which are being investigated in clinical trials for their immunomodulatory potential. hESC-MSC have the advantage of being consistent because each batch can be generated from hESC under defined conditions. In contrast, BM-MSC have a limited proliferative capacity.
The ability to suppress the proliferation of anti-CD3/CD28-stimulated CD4 (+) T cells by hESC-MSC was compared with adult BM-MSC and neonatal foreskin fibroblast (Fb).
hESC-MSC suppress the proliferation of CD4 (+) T cells in both contact and transwell systems, although inhibition is less in the transwell system. hESC-MSC are approximately 2-fold less potent (67 cells/100 T cells) than BM-MSC and Fb (37 and 34 cells/100 T cells, respectively) at suppressing T-cell proliferation by 50% in a transwell [inhibitory concentration(IC)(50)]. The anti-proliferative effect is not contact-dependent but requires the presence of factors such as interferon (IFN)-γ produced by activated T cells. IFN-γ induces the expression of indoleamine-2,3-dioxygenase (IDO) in hESC-MSC, BM-MSC and Fb, contributing to their immunosuppressive property.
The feedback loop between MSC or Fb and activated T cells may limit the immunosuppressive effects of MSC and Fb to sites containing ongoing immunologic or inflammatory responses where activated T cells induce the up-regulation of IDO and immunomodulatory properties of MSC and Fb. These data demonstrate that hESC-MSC may be evaluated further as an allogeneic cell source for therapeutic applications requiring immunosuppression.
人胚胎干细胞（hESC）衍生的间充质基质细胞（MSC）（hESC-MSC）是骨髓（BM）衍生 MSC（BM-MSC）的替代来源，目前正在临床试验中研究其免疫调节潜力。hESC-MSC 的优势在于一致性，因为每一批都可以在定义的条件下从 hESC 中产生。相比之下，BM-MSC 的增殖能力有限。
比较了 hESC-MSC 抑制抗 CD3/CD28 刺激的 CD4（+）T 细胞增殖的能力与成人 BM-MSC 和新生儿包皮成纤维细胞（Fb）。
hESC-MSC 在接触和 Transwell 系统中均抑制 CD4（+）T 细胞的增殖，尽管在 Transwell 系统中抑制作用较弱。hESC-MSC 抑制 T 细胞增殖的效力约为 BM-MSC 和 Fb 的一半（在 Transwell 中抑制 50%增殖的浓度[IC（50）]，分别为 67 个细胞/100T 细胞和 37 个细胞/100T 细胞和 34 个细胞/100T 细胞）。这种抗增殖作用不是依赖接触的，而是需要 T 细胞激活后产生的干扰素（IFN）-γ等因子的存在。IFN-γ诱导 hESC-MSC、BM-MSC 和 Fb 中吲哚胺 2,3-双加氧酶（IDO）的表达，这有助于它们的免疫抑制特性。
MSC 或 Fb 与激活的 T 细胞之间的反馈回路可能会限制 MSC 和 Fb 的免疫抑制作用仅限于包含持续免疫或炎症反应的部位，在这些部位，激活的 T 细胞诱导 IDO 的上调以及 MSC 和 Fb 的免疫调节特性。这些数据表明，hESC-MSC 可进一步评估为需要免疫抑制的治疗应用的同种异体细胞来源。
