Comparison of mesenchymal stem cells from different tissues to suppress T-Cell activation
Comparison of mesenchymal stem cells from different tissues to suppress T-Cell activation
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DOI：
10.3727/000000007783464939
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Kiem, Hans-Peter
中科院分区：
文献类型：
--
作者：
Keyser, Kirsten A.;Beagles, Karen E.;Kiem, Hans-Peter
移植物抗宿主病（GvHD）和移植物排斥反应仍然是同种异体干细胞移植的重要并发症。来自骨髓的间充质干细胞（MSCs）已被证明可以抑制体内和体外的t细胞活化，并可用于降低受体的GvHD或促进跨越MHC屏障的移植。间充质干细胞可以来源于多种组织。因此，我们询问来自不同组织的间充质干细胞是否可能对t细胞反应有不同的影响。我们对来源于脂肪组织的间充质干细胞特别感兴趣，因为它的丰度和可获得性。我们研究并比较了来自肌肉组织、脂肪组织、网膜和骨骼的小鼠间充质干细胞的免疫抑制潜力。将来自不同组织的细胞富集为MSCs，并培养2-3周以耗尽造血细胞。混合淋巴细胞反应（MLRs）包括间充质干细胞使用豆豆蛋白A或同种异体T细胞作为T细胞活化的诱导剂。来自所有组织的MSCs分化成多个谱系。在MSCs介导的MLRs中，丝裂原诱导的t细胞活化以及同种异体t细胞反应被降低。在同种异体MLR中，有丝分裂原诱导的MLR中肌肉组织和脂肪组织的t细胞活化减少最为明显。这些数据表明，来自多个组织的间充质干细胞可以有效地降低t细胞的活化。结果表明，来自脂肪组织的间充质干细胞可以作为骨或骨髓间充质干细胞的替代来源，用于调节同种异体干细胞移植后的GvHD或增强跨越MHC屏障的植入。
Graft-versus-host disease (GvHD) and graft rejection have remained significant complications of allogeneic stem cell transplantation. Mesenchymal stem cells (MSCs) from the bone marrow have been shown to suppress T-cell activation in vitro and in vivo, and may be used to reduce GvHD in the recipient or to facilitate engraftment across MHC barriers. MSCs can be derived from a variety of tissues. Thus, we asked whether MSCs from different tissues might have differential effects on T-cell responses. We were particularly interested in MSCs derived from adipose tissue because of its abundance and accessibility. We investigated and compared the immunosuppressive potential of murine MSCs derived from muscle tissue, adipose tissue, omentum, and bone. Cells from the different tissues were enriched for MSCs and cultured for 2-3 weeks to deplete hematopoietic cells. Mixed lymphocyte reactions (MLRs) including MSCs were performed using concanavalin A or allogeneic T cells as inducers of T-cell activation. MSCs from all tissues differentiated into multiple lineages. Mitogen-induced T-cell activation, as well as allogeneic T-cell responses, was reduced in MLRs mediated by the addition of MSCs. Reduction of T-cell activation was most pronounced for muscle tissue in the mitogen-induced MLR and fat tissue during the allogeneic MLR. These data demonstrate that MSCs from multiple tissues efficiently reduce T-cell activation. The results suggest that MSCs from adipose tissue can serve as an alternative source for MSCs to bone or bone marrow for the modulation of GvHD after allogeneic stem cell transplantation or to enhance engraftment across MHC barriers.