Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
Clin Immunol. 2012 Nov;145(2):142-52. doi: 10.1016/j.clim.2012.08.012. Epub 2012 Sep 17.
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 naïve 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.
间充质干细胞（MSC）被探索作为治疗系统性红斑狼疮（SLE）的一种有前途的新方法。在本研究中，我们：1）评估同种异体与同基因 MSC 移植对狼疮样疾病的差异影响，2）探索 MSC 调节疾病的机制，3）研究狼疮来源的 MSC 是否存在固有免疫调节缺陷。我们发现，在 MRL/lpr 小鼠和（NZB/NZW）F1 小鼠中，B6-MSC 和来自年轻小鼠的狼疮 MSC 均改善了狼疮样疾病，并减少了脾脏 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 并未显著减少脾脏重量、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 移植通过减少 CD4+T 细胞和幼稚成熟 B 细胞的数量部分改善狼疮样疾病。鉴于狼疮来源的 MSC 总体效果降低，同种异体 MSC 可能优于同基因狼疮来源的 MSC，这部分归因于疾病，而不仅仅是 MSC 本身的固有缺陷。
