Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo
Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo
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DOI：
10.1016/s0301-472x(01)00769-x
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发表时间：
2002-01-01
影响因子：
2.6
通讯作者：
Hoffman, R
中科院分区：
文献类型：
--
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
客观的。可以诱导驻留在骨髓内的多稳态细胞的间充质干细胞（MSC）分化成骨髓微环境的各种成分，例如骨，脂肪和基质组织。骨髓微环境对于淋巴结瘤系统的发育，分化和调节至关重要。我们假设MSC在骨髓微环境中的活性也可能包括对淋巴细胞的免疫调节作用。在体外测试了狒狒MSC，其能够从同种异体淋巴细胞中引起增生反应，抑制持续的同种异体反应，并抑制对有效的T细胞有效的T-Cell促毒素的增殖反应。在放置自体，供体和第三方皮肤移植物之前，通过静脉内给予MHC不匹配的接受者狒狒对体内效应进行了体内效应。 MSC未能引起同种异体淋巴细胞的增生反应。 MSC在第0天或第3天加入混合淋巴细胞反应，或促成有丝分裂原刺激的淋巴细胞，导致增殖活性降低了50％以上。可以通过升级MSC的剂量来最大化这种效果，并且可以通过添加外源性IL-2来降低这种效果。与对照动物相比，在体内给药MSC导致了长时间的皮肤移植物存活率：11.3 +/- 0.3 vs 7 +/- 0.conconclusions。已经观察到狒狒MSC改变了对同种异体靶细胞和组织的淋巴细胞反应性。这些免疫调节特征可能在组织再生和干细胞工程的未来应用中很有用。 （c）2002年国际实验血液学学会。由Elsevier Science Inc.出版
Objective. Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various components of the marrow microenvironment, such as bone, adipose, and stromal tissues. The bone marrow micro environment is vital to the development, differentiation, and regulation of the lymphohematopoietic system. We hypothesized that the activities of MSCs in the bone marrow microenvironment might also include immunomodulatory effects on lymphocytes.Methods. Baboon MSCs were tested in vitro for their ability to elicit a proliferative response from allogeneic lymphocytes, to inhibit an ongoing allogeneic response, and to inhibit a proliferative response to potent T-cell mitogens. In vivo effects were tested by intravenous administration of donor MSCs to MHC-mismatched recipient baboons prior to placement of autologous, donor, and third-party skin grafts.Results. MSCs failed to elicit a proliferative response from allogeneic lymphocytes. MSCs added into a mixed lymphocyte reaction, either on day 0 or on day 3, or to mitogen-stimulated lymphocytes, led to a greater than 50% reduction in proliferative activity. This effect could be maximized by escalating the dose of MSCs and could be reduced with the addition of exogenous IL-2. In vivo administration of MSCs led to prolonged skin graft survival when compared to control animals: 11.3 +/- 0.3 vs 7 +/- 0.Conclusions. Baboon MSCs have been observed to alter lymphocyte reactivity to allogeneic target cells and tissues. These immunoregulatory features may prove useful in future applications of tissue regeneration and stem cell engineering. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.