Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation
Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation
复制标题
DOI：
10.1038/sj.bmt.1704400
复制
发表时间：
2004-03-01
影响因子：
4.8
通讯作者：
Koç, O
中科院分区：
文献类型：
--
作者：
Maitra, B;Szekely, E;Koç, O
骨髓间充质干细胞(MSCs)可与造血干细胞(HSCs)和免疫细胞相互作用，是促进异基因造血植入和预防移植物抗宿主病(GVHD)的潜在细胞疗法。我们研究了人骨髓间充质干细胞在非血缘关系的人造血细胞对NOD-SCID小鼠再繁殖中的作用，并研究了人骨髓间充质干细胞与非血缘关系供者血细胞之间的免疫相互作用。当造血干细胞数量有限时，NOD-SCID小鼠只有在输注无关的人MSCs后才能观察到人的植入，而不能观察到与小鼠间充质细胞系共输注的人移植。无血缘关系的人MSCs在体外不能诱导T细胞激活，并以剂量依赖的方式抑制结核菌素和无关同种异体淋巴细胞对T细胞的激活。无细胞MSC培养上清、小鼠基质细胞和人真皮成纤维细胞均不能诱导这种效应。这些临床前数据表明，无关的人骨髓来源的培养扩增的MSCs可能通过促进造血植入和限制GVHD来改善异基因移植的结果，其治疗潜力有待临床检验。
Bone marrow-derived mesenchymal stem cells (MSCs) are known to interact with hematopoietic stem cells (HSCs) and immune cells, and represent potential cellular therapy to enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease (GVHD). We investigated the role of human MSCs in NOD-SCID mice repopulation by unrelated human hematopoietic cells and studied the immune interactions between human MSCs and unrelated donor blood cells in vitro. When hematopoietic stem cell numbers were limited, human engraftment of NOD-SCID mice was observed only after coinfusion of unrelated human MSCs, but not with coinfusion of mouse mesenchymal cell line. Unrelated human MSCs did not elicit T-cell activation in vitro and suppressed T-cell activation by Tuberculin and unrelated allogeneic lymphocytes in a dose-dependent manner. Cell-free MSC culture supernatant, mouse stromal cells and human dermal fibroblasts did not elicit this effect. These preclinical data suggest that unrelated, human bone marrow-derived, culture-expanded MSCs may improve the outcome of allogeneic transplantation by promoting hematopoietic engraftment and limiting GVHD and their therapeutic potential should be tested in clinic.