Human mesenchymal stem cells modulate allogeneic immune cell responses
Human mesenchymal stem cells modulate allogeneic immune cell responses
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DOI：
10.1182/blood-2004-04-1559
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发表时间：
2005-02-15
期刊：
影响因子：
20.3
通讯作者：
Pittenger, MF
中科院分区：
文献类型：
--
作者：
Aggarwal, S;Pittenger, MF
间充质干细胞（MSC）是在几种成人组织中发现的多能细胞。移植的同种异体间充质干细胞可以在延长的时间点在受体中检测到，表明缺乏免疫识别和清除。同样，最近有报道称骨髓来源的MSC在同种异体移植过程中降低移植物抗宿主病（GVHD）的发生率和严重程度;然而，其机制仍有待研究。我们通过将人骨髓间充质干细胞（hMSCs）与纯化的免疫细胞亚群共培养来检测其免疫调节功能，并在此报告hMSCs改变了树突状细胞（DCs）、初始和效应T细胞（T辅助细胞1 [T（H）1]和T（H）2）以及自然杀伤（NK）细胞的细胞因子分泌谱，以诱导更具抗炎性或耐受性的表型。具体地说，hMSC引起成熟的DC 1型（DC 1）减少肿瘤坏死因子α（TNF α），（TNIF-alpha）分泌和成熟DC 2以增加白细胞介素-10（IL-10）分泌; hMSC引起TO细胞减少干扰素γ hMSC引起存在的调节性T细胞（T-Reg）的比例增加; hMSC减少NK细胞分泌IFN-γ。从机制上讲，hMSC在共培养物中产生升高的前列腺素E2（PGE（2）），PGE（2）产生的抑制剂减轻了hMSC介导的免疫调节。这些数据提供了对同种异体MSC和免疫细胞之间的相互作用的深入了解，并提供了可能涉及体内MSC介导的耐受诱导的机制，其可以用于治疗GVHD、排斥和炎症的调节。(C)2005年，美国血液学会。
Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus-host disease (GVHD) during allogenelc transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immunomodulatory functions of human MSCs (hMSCs) by coculturing them with purified subpopulations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [T(H)1] and T(H)2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DCs type 1 (DC1) to decrease tumor necrosis factor alpha (TNIF-alpha) secretion and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused TO cells to decrease interferon gamma (IFN-gamma) and caused the TH2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (T-Regs) present; and hMSCs decreased secretion of IFN-gamma from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2 (PGE(2)) in co-cultures, and inhibitors of PGE(2) production mitigated hMSC-mediated immune modulation. These data offer insight into the interactions between allogeneic MSCs and immune cells and provide mechanisms likely involved with the in vivo MSC,mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation. (C) 2005 by The American Society of Hematology.