Human iPSC-Derived Neural Crest Stem Cells Exhibit Low Immunogenicity
Human iPSC-Derived Neural Crest Stem Cells Exhibit Low Immunogenicity
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DOI：
10.1016/j.omtm.2019.12.015
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发表时间：
2020-03-13
影响因子：
4.7
通讯作者：
Moore, Melanie L.
中科院分区：
文献类型：
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作者：
Mehler, Vera J.;Burns, Chris J.;Moore, Melanie L.
最近的临床试验正在评估诱导多能干细胞（iPSC）作为再生医学领域的细胞疗法。iPSC的广泛临床应用预计将使用经过彻底安全性评估（包括其免疫原性评估）的同种异体细胞来实现。IPSC衍生的神经嵴干细胞（NCSC）在再生医学中具有显著的潜力;然而，迄今为止，它们在细胞治疗中的应用尚未被广泛研究，并且迄今为止还没有关于其潜在免疫原性的报道。在这项研究中，我们评估了iPSC-NCSC中免疫相关抗原的表达，包括人类白细胞抗原（HLA）I类和II类以及共刺激分子。为了研究功能性免疫原性，我们在单向混合淋巴细胞反应中使用iPSC-NCSC作为刺激细胞。在这些实验中，iPSC-NCSC没有刺激可检测的CD 3（+）和CD 3（+）CD 8（+）T细胞增殖或诱导细胞因子产生。我们表明，这不是iPSC-NCSC的任何免疫抑制特征的结果，而是与其非免疫原性分子表型更一致。这些结果对于iPSC-NCSC作为细胞疗法的潜在未来用途是令人鼓舞的。
Recent clinical trials are evaluating induced pluripotent stem cells (iPSCs) as a cellular therapy in the field of regenerative medicine. The widespread clinical utility of iPSCs is expected to be realized using allogeneic cells that have undergone thorough safety evaluations, including assessment of their immunogenicity. IPSC-derived neural crest stem cells (NCSCs) have significant potential in regenerative medicine; however, their application in cellular therapy has not been widely studied to date, and no reports on their potential immunogenicity have been published so far. In this study, we have assessed the expression of immune-related antigens in iPSC-NCSCs, including human leukocyte antigen (HLA) class I and II and co-stimulatory molecules. To investigate functional immunogenicity, we used iPSC-NCSCs as stimulator cells in a oneway mixed lymphocyte reaction. In these experiments, iPSC-NCSCs did not stimulate detectable proliferation of CD3(+) and CD3(+)CD8(+) T cells or induce cytokine production. We show that this was not a result of any immunosuppressive features of iPSC-NCSCs, but rather more consistent with their non-immunogenic molecular phenotype. These results are encouraging for the potential future use of iPSC-NCSCs as a cellular therapy.