Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans.
Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans.
复制标题
间充质干细胞移植可逆转系统性红斑狼疮小鼠和人类的多器官功能障碍
DOI：
10.1002/stem.68
复制
发表时间：
2009-06
期刊：
影响因子：
5.2
通讯作者：
Shi, Songtao
中科院分区：
文献类型：
--
作者：
Sun, Lingyun;Akiyama, Kentaro;Zhang, Huayong;Yamaza, Takayoshi;Hou, Yayi;Zhao, Shengnan;Xu, Ting;Le, Anh;Shi, Songtao
系统性红斑狼疮(SLE)是一种多系统自身免疫性疾病，尽管免疫抑制药物治疗取得了进展，但在一些患者，特别是在治疗难治的患者中，仍具有潜在的致命性。在这里，我们报道了骨髓间充质干细胞(BMMSCs)的损伤及其相关的成骨细胞生态位缺陷在一定程度上导致了MRL/LPR小鼠SLE样疾病的发病。有趣的是，与环磷酰胺(CTX)的药物免疫抑制相比，同种异体骨髓间充质干细胞移植(MSCT)能够重建骨髓成骨细胞生态位，并更有效地逆转多器官功能障碍。在细胞水平上，MSCT而不是CTX治疗能够诱导成骨细胞生态位重建，可能有助于调节性T细胞的恢复和免疫稳态的重建。基于在SLE小鼠身上有希望的临床结果，我们使用同种异体MSCT治疗了4名CTX/糖皮质激素治疗难治性SLE患者，所有接受治疗的患者都显示出稳定的12-18个月的疾病缓解。患者的病情活动度、血清标志物和肾功能均有改善。这些早期证据表明，同种异体MSCT可能是难治性SLE患者一种可行且安全的抢救治疗方法。
Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease that, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. Here we reported that impairment of bone marrow mesenchymal stem cells (BMMSCs) and their associated osteoblastic niche deficiency contribute in part to the pathogenesis of SLE-like disease in MRL/lpr mice. Interestingly, allogenic BMMSC transplantation (MSCT) is capable of reconstructing the bone marrow osteoblastic niche and more effectively reverses multi-organ dysfunction as compared to medical immunosuppression with cyclophosphamide (CTX). At the cellular level, MSCT, not CTX treatment, was capable to induce osteoblastic niche reconstruction, possibly contributing to the recovery of regulatory T cells and re-establishment of the immune homeostasis. Based on the promising clinical outcomes in SLE mice, we treated 4 CTX/glucocorticoid treatment-refractory SLE patients using allogenic MSCT and showed a stable 12-18 months disease remission in all treated patients. The patients benefited an amelioration of disease activity, improvement in serologic markers and renal function. These early evidences suggest that allogenic MSCT may be a feasible and safe salvage therapy in refractory SLE patients.
登录
查看更多内容
DOI：
10.1073/pnas.90.21.10340
发表时间：
1993-11-01
影响因子：
11.1
作者：
DRAPPA, J;BROT, N;ELKON, KB
通讯作者：
ELKON, KB
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF
影响因子：
6.2
作者：
FRIEDENSTEIN, AJ;CHAILAKHYAN, RK;KEILISSB.IV
通讯作者：
KEILISSB.IV