MHC Mismatch Inhibits Neurogenesis and Neuron Maturation in Stem Cell Allografts
MHC Mismatch Inhibits Neurogenesis and Neuron Maturation in Stem Cell Allografts
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DOI：
10.1371/journal.pone.0028618
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发表时间：
2011-03-30
期刊：
影响因子：
3.7
通讯作者：
Palmer, Theo D.
中科院分区：
文献类型：
--
作者：
Chen, Zhiguo;Phillips, Lori K.;Palmer, Theo D.
背景：组织相容性和免疫识别在干细胞移植治疗中的作用一直存在争议，许多报告认为，由于缺乏主要组织相容性复合体（MHC）标记，未分化干细胞免受免疫识别。这一论点在移植到中枢神经系统 (CNS) 时更具说服力，因为中枢神经系统的移植物排斥反应很小。 方法/主要发现：在这项研究中，我们评估了移植到小鼠海马体中的完全匹配与严重不匹配的神经干细胞的移植物存活和神经元生成。尽管同种异体细胞能够存活，但我们观察到 MHC 错配会减少存活细胞数量，并强烈抑制移植物来源以及内源产生的新神经元的分化和保留。使用环孢素 A 进行免疫抑制并不能改善结果，但非甾体类抗炎药吲哚美辛或罗格列酮能够将同种异体神经元的产生、整合和保留恢复到同基因移植物的水平。结论/意义：这些结果表明，先天免疫而非适应性免疫在 CNS 中 MHC 不匹配的细胞移植物的存活和功能中发挥着重要但未被怀疑的作用。
Background: The role of histocompatibility and immune recognition in stem cell transplant therapy has been controversial, with many reports arguing that undifferentiated stem cells are protected from immune recognition due to the absence of major histocompatibility complex (MHC) markers. This argument is even more persuasive in transplantation into the central nervous system (CNS) where the graft rejection response is minimal.Methodology/Principal Findings: In this study, we evaluate graft survival and neuron production in perfectly matched vs. strongly mismatched neural stem cells transplanted into the hippocampus in mice. Although allogeneic cells survive, we observe that MHC-mismatch decreases surviving cell numbers and strongly inhibits the differentiation and retention of graft-derived as well as endogenously produced new neurons. Immune suppression with cyclosporine-A did not improve outcome but non-steroidal anti-inflammatory drugs, indomethacin or rosiglitazone, were able to restore allogeneic neuron production, integration and retention to the level of syngeneic grafts.Conclusions/Significance: These results suggest an important but unsuspected role for innate, rather than adaptive, immunity in the survival and function of MHC-mismatched cellular grafts in the CNS.