Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue.
Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue.
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DOI：
10.1089/scd.2013.0043
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发表时间：
2013-05
影响因子：
4
通讯作者：
M. Stubbendorff;T. Deuse;X. Hua;T. T. Phan-T.;K. Bieback;Kerry Atkinson;T. Eiermann;J. Velden;C. Schröder;H. Reichenspurner;R. Robbins;H. Volk;S. Schrepfer
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文献类型：
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作者：
M. Stubbendorff;T. Deuse;X. Hua;T. T. Phan-T.;K. Bieback;Kerry Atkinson;T. Eiermann;J. Velden;C. Schröder;H. Reichenspurner;R. Robbins;H. Volk;S. Schrepfer
间充质间质细胞（MSCs）已经从许多组织中分离出来，包括妊娠组织。迄今为止，缺乏比较这些细胞在细胞基础疗法中的特性和适用性的研究。在这项研究中，我们比较了来自脐带衬里（CL-MSCs）、脐带血（CB-MSCs）、胎盘（P-MSCs）和沃顿果冻（WJ-MSCs）的人间充质干细胞的表型、增殖率、迁移、免疫原性和免疫调节能力。在分化、增殖和迁移方面存在差异，在免疫缺陷小鼠中，CL-MSCs表现出最高的增殖和迁移率，从而延长了存活时间。此外，CL-MSCs在异种BALB/c小鼠中显示出延长生存的能力，这归因于它们抑制TH1和TH2反应的能力。CL-MSCs和P-MSCs的人细胞免疫应答较弱，这与它们较低的HLA - I表达有关。此外，在IFN-γ刺激后，CL-MSCs和CB-MSCs的HLA II上调幅度较小。IFN-γ刺激后，间充质干细胞类型的吲哚胺2,3-双加氧酶（IDO）表达无差异。尽管其IDO、HLA-G和TGF-β1的表达较低，但只有CL-MSCs能够在混合淋巴细胞反应中减少淋巴细胞释放IFN-γ。总之，CL-MSCs表现出基于细胞的策略的最佳特性，因为它们是低免疫原性的，具有高增殖和迁移率。此外，这些研究首次表明，尽管免疫调节分子HLA- g、HLA- e和TGF-β在间充质干细胞的免疫逃避中发挥重要作用，但基础和诱导的HLA表达似乎是决定间充质干细胞免疫原性的决定性因素。
Mesenchymal stromal cells (MSCs) have been isolated from many tissues, including gestational tissue. To date, a study comparing the properties and suitability of these cells in cell-based therapies is lacking. In this study, we compared the phenotype, proliferation rate, migration, immunogenicity, and immunomodulatory capabilities of human MSCs derived from umbilical cord lining (CL-MSCs), umbilical cord blood (CB-MSCs), placenta (P-MSCs), and Wharton's jelly (WJ-MSCs). Differences were noted in differentiation, proliferation, and migration, with CL-MSCs showing the highest proliferation and migration rates resulting in prolonged survival in immunodeficient mice. Moreover, CL-MSCs showed a prolongation in survival in xenogeneic BALB/c mice, which was attributed to their ability to dampen TH1 and TH2 responses. Weaker human cellular immune responses were detected against CL-MSCs and P-MSCs, which were correlated with their lower HLA I expression. Furthermore, HLA II was upregulated less substantially by CL-MSCs and CB-MSCs after IFN-γ stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-γ stimulation. Despite their lower IDO, HLA-G, and TGF-β1 expression, only CL-MSCs were able to reduce the release of IFN-γ by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cell-based strategies, as they are hypo-immunogenic and show high proliferation and migration rates. In addition, these studies show for the first time that although immunomodulatory molecules HLA-G, HLA-E, and TGF-β play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.