Schnabel Lauren V, Abratte Christian M, Schimenti John C, Felippe M Julia Bevilaqua, Cassano Jennifer M, Southard Teresa L, Cross Jessica A, Fortier Lisa A
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
Regen Med. 2014;9(5):621-35. doi: 10.2217/rme.14.29. Epub 2014 Apr 28.
To evaluate the in vitro immunogenic and immunomodulatory properties of induced pluripotent stem cells (iPSCs) compared with bone marrow-derived mesenchymal stromal cells (MSCs).
MATERIALS & METHODS: Mouse embryonic fibroblasts (MEFs) were isolated from C3HeB/FeJ and C57BL/6J mice, and reprogrammed to generate iPSCs. Mixed leukocyte reactions were performed using MHC-matched and -mismatched responder leukocytes and stimulator leukocytes, iPSCs or MSCs. To assess immunogenic potential, iPSCs and MSCs were used as stimulator cells for responder leukocytes. To assess immunomodulatory properties, iPSCs and MSCs were cultured in the presence of stimulator and responder leukocytes. MEFs were used as a control.
iPSCs had similar immunogenic properties but more potent immunomodulatory effects than MSCs. Co-culture of MHC-mismatched leukocytes with MHC-matched iPSCs resulted in significantly less responder T-cell proliferation than observed for MHC-mismatched leukocytes alone and at more responder leukocyte concentrations than with MSCs. In addition, MHC-mismatched iPSCs significantly reduced responder T-cell proliferation when co-cultured with MHC-mismatched leukocytes, while MHC-mismatched MSCs did not.
These results provide important information when considering the use of iPSCs in place of MSCs in both regenerative and transplantation medicine.
评估诱导多能干细胞（iPSC）与骨髓来源的间充质基质细胞（MSC）相比的体外免疫原性和免疫调节特性。
从小鼠C3HeB/FeJ和C57BL/6J中分离出小鼠胚胎成纤维细胞（MEF），并将其重编程以生成iPSC。使用主要组织相容性复合体（MHC）匹配和不匹配的反应性白细胞以及刺激性白细胞、iPSC或MSC进行混合白细胞反应。为评估免疫原性潜力，将iPSC和MSC用作反应性白细胞的刺激细胞。为评估免疫调节特性，将iPSC和MSC在刺激性和反应性白细胞存在下进行培养。将MEF用作对照。
iPSC具有与MSC相似的免疫原性特性，但免疫调节作用更强。与仅观察到的MHC不匹配的白细胞相比，MHC不匹配的白细胞与MHC匹配的iPSC共培养导致反应性T细胞增殖明显减少，且在比与MSC共培养时更高的反应性白细胞浓度下也是如此。此外，当与MHC不匹配的白细胞共培养时，MHC不匹配的iPSC显著降低反应性T细胞增殖，而MHC不匹配的MSC则没有。
在考虑在再生医学和移植医学中使用iPSC替代MSC时，这些结果提供了重要信息。
