What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?
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DOI:
10.1155/2015/583984
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发表时间:
2015
影响因子:
4.3
通讯作者:
Cruz PE
Cruz PE
中科院分区:
医学3区
文献类型:
--
作者:
Bárcia RN;Santos JM;Filipe M;Teixeira M;Martins JP;Almeida J;Água-Doce A;Almeida SC;Varela A;Pohl S;Dittmar KE;Calado S;Simões SI;Gaspar MM;Cruz ME;Lindenmaier W;Graça L;Cruz H;Cruz PE

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来自脐带组织的MSCs(称为UCX)被研究了其免疫调节特性,并与免疫治疗的金标准骨髓来源的MSCs (BM-MSCs)进行了比较。通过混合淋巴细胞反应、抑制淋巴细胞增殖和诱导调节性T细胞来评估免疫原性和免疫抑制。结果表明,与BM-MSCs相比,UCX具有较低的免疫原性和较高的免疫抑制活性。此外,UCX不需要事先激活或启动来发挥其免疫调节作用。这在体内急性炎症模型中得到进一步证实。为了阐明在UCX和BM-MSCs之间观察到的效力差异,分析了两种细胞类型中与免疫调节相关的基因表达。UCX和BM-MSCs之间存在多个基因表达谱差异,即HLA-DRA、HO-1、IGFBP1、4和6、ILR1、IL6R和PTGES的表达降低,CD200、CD273、CD274、IL1B、IL-8、LIF和TGFB2的表达升高。后者在蛋白表达水平得到证实。总的来说,这些结果表明,UCX似乎天然比BM-MSCs更有效的免疫抑制剂和更低的免疫原性。我们认为,这些差异可能是由于免疫调节表面蛋白(如CD200、CD273、CD274)和细胞因子(如il - 1β、IL-8、LIF和tgf - β2)水平的增加。
MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.
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