Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation
Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation
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DOI：
10.1111/j.1582-4934.2009.00657.x
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发表时间：
2009-08-01
影响因子：
5.3
通讯作者：
Lescaudron, Laurent
中科院分区：
文献类型：
--
作者：
Rossignol, Julien;Boyer, Cecile;Lescaudron, Laurent
间充质干细胞（MSC）因其在脑移植等再生医学中的潜在用途而引起人们的关注。由于MSC被认为是低免疫原性的，因此移植的MSC不应引发强烈的宿主炎症反应。为了验证这一假设，我们研究了将人或大鼠MSC移植到大鼠纹状体后的脑免疫应答以及移植后第5、14、21和63天的MSC命运。流式细胞仪分析表明，这两种MSC表达CD 90和人白细胞抗原（MHC）I类分子，但没有MHC II类分子。它们不表达CD 45或CD 34抗原。然而，MSC表型随传代次数而变化。人MSC具有白细胞介素（IL）-6、IL-8、IL-12、肿瘤坏死因子（TNF）-α和TGF-β（1）的mRNA，而大鼠MSC表达IL-6-、IL-10-、IL-12-和TGF-β（1）-mRNA。定量显示抗炎分子IL-6和TGF-β（1）的mRNA水平高于促炎细胞因子IL-8和IL-12; ELISA分析显示没有IL-12，而检测到TGF-β（1）和IL-6。移植后14至63天，移植物大小无显著变化，表明移植物无免疫排斥反应。在大鼠和人MSC移植物中，在移植后第5天观察到的极少数肥大细胞和中度巨噬细胞和小胶质细胞浸润保持稳定，直到第63天。观察到非常少的树突状细胞、T α β细胞和没有T γ δ淋巴细胞，所有这三种细胞都与脑中的Tp排斥有关，这支持了MSC是低免疫原性的论点。我们的研究结果表明，骨髓间充质干细胞在再生医学（异种）移植设置的极大兴趣。
Mesenchymal stem cells (MSCs) have attracted attention for their potential use in regenerative medicine such as brain transplantation. As MSCs are considered to be hypoimmunogenic, transplanted MSCs should not trigger a strong host inflammatory response. To verify this hypothesis, we studied the brain immune response after transplantation of human or rat MSCs into the rat striatum and MSC fate at days 5, 14, 21 and 63 after transplantation. Flow cytometry analysis indicated that both MSCs express CD90 and human leucocyte antigen (MHC) class I, but no MHC class II molecules. They do not express CD45 or CD34 antigens. However, MSC phenotype varies with passage number. Human MSCs have mRNAs for interleukin (IL)-6, IL-8, IL-12, tumour necrosis factor (TNF)-alpha and TGF-beta(1), whereas rat MSCs express IL-6-, IL-10-, IL-12- and TGF-beta(1)-mRNAs. The quantification shows higher levels of mRNAs for the anti-inflammatory molecules IL-6 and TGF-beta(1) than for pro-inflammatory cytokines IL-8 and IL-12; ELISA analysis showed no IL-12 whereas TGF-beta(1) and IL-6 were detected. Transplant size did not significantly vary between 14 and 63 days after transplantation, indicating an absence of immune rejection of the grafts. Very few mast cells and moderate macrophage and microglial infiltrations, observed at day 5 remained stable until day 63 after transplantation in both rat and human MSC grafts. The observations of very few dendritic cells, T alpha beta-cells, and no T gamma delta-lymphocytes, all three being associated with Tp rejection in the brain, support the contention that MSCs are hypoimmunogenic. Our results suggest that MSCs are of great interest in regenerative medicine in a (xeno)transplantation setting.