Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice
Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice
复制标题
DOI：
10.1016/j.clim.2012.08.012
复制
发表时间：
2012-11-01
影响因子：
8.6
通讯作者：
Gilkeson, Gary S.
中科院分区：
文献类型：
--
作者：
Gu, Fei;Molano, Ivan;Gilkeson, Gary S.
MSC 正在被探索作为一种有前途的 SLE 新型治疗方法。在这项研究中，我们：1) 评估了同种异体与同基因 MSC 移植对狼疮样疾病的不同影响，2) 探索 MSC 调节疾病的机制，3) 研究狼疮衍生的 MSC 是否具有内在的免疫调节缺陷。我们发现，在 MRL/lpr 小鼠和 (NZB/NZW)F1 小鼠中，来自年轻小鼠的 B6-MSC 和狼疮-MSC 均改善了 SLE 样疾病，并减少了脾 CD3+CD4+ T 淋巴细胞和 CD19+CD21+ B 淋巴细胞。然而，来自老年 (NZB/NZW)F1 小鼠的狼疮-MSC 并未显着降低脾脏重量、肾小球 IgG 沉积、肾脏病理、间质炎症、CD3+CD4+ T 淋巴细胞或 CD19+CD21+ B 淋巴细胞。因此，MSC 移植部分通过减少 CD4+ T 细胞和幼稚成熟 B 细胞数量来改善 SLE 样疾病。鉴于狼疮后衍生 MSC 的整体有效性下降，同种异体 MSC 可能优于同基因狼疮衍生 MSC，这部分是由于疾病所致，而不仅仅是 MSC 本身的内在缺陷。由爱思唯尔公司出版
MSC are being explored as a promising novel treatment for SLE. In this study, we: 1) assessed the differential effects of allogeneic versus syngeneic MSC transplantation on lupus-like disease, 2) explored the mechanisms by which MSC modulate disease, and 3) investigated whether lupus-derived-MSC have intrinsic immunomodulatory defects. We showed that in MRL/lpr mice and (NZB/NZW)F1 mice, both B6-MSC and lupus-MSC from young mice ameliorated SLE-like disease and reduced splenic CD3+CD4+ T lymphocytes and CD19+CD21+ B lymphocytes. However, lupus-MSC from older (NZB/NZW)F1 mice did not reduce spleen weights, glomerular IgG deposits, renal pathology, interstitial inflammation, CD3+CD4+ T lymphocytes or CD19+CD21+ B lymphocytes significantly. Thus MSC transplantation ameliorates SLE-like disease partly through decreasing CD4+ T cell and naive mature B cell numbers. Allogeneic MSC may be preferred over syngeneic lupus-derived-MSC given the decreased overall effectiveness of post-lupus-derived-MSC, which appears partially due to disease and not exclusively intrinsic defects in the MSC themselves. Published by Elsevier Inc.