Mesenchymal Stem Cells Attenuate Rat Graft-Versus-Host Disease

Mesenchymal Stem Cells Attenuate Rat Graft-Versus-Host Disease
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间充质干细胞减轻大鼠移植物抗宿主病

DOI:
10.1007/978-1-4939-1453-1_28
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发表时间:
2014-01-01
期刊:
ANIMAL MODELS FOR STEM CELL THERAPY
影响因子:
--
通讯作者:
Li, Xiao-Kang
Li, Xiao-Kang
中科院分区:
其他
文献类型:
--
作者:
Fujino, Masayuki;Zhu, Ping;Li, Xiao-Kang

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来源于骨髓的间充质干细胞(MSC)具有强大的免疫调节作用,因此在T淋巴细胞依赖性疾病中具有治疗潜力。目前的文章旨在描述的方法来调查,骨髓间充质干细胞可能会利用调节移植物抗宿主病(GvHD),发病率和致死率后异基因造血干细胞移植(HSCT)的主要病因。从刘易斯大鼠骨髓中分离MSC并培养4周。通过autoMACS实现富集的常规MSC和巨噬细胞的纯化。使用有限稀释法,克隆MSC,然后扩增至6个月以上。培养的MSCs呈典型的梭形形态和免疫表型,不表达CD 45和CD 11b/c。MSC也以其分化成脂肪细胞的能力而闻名。与巨噬细胞一样,MSC表现出抑制T淋巴细胞增殖的免疫调节倾向。继过继转移后,MSC调节全身刘易斯至(刘易斯× DA)F1大鼠GvHD。同时,克隆的MSC令人惊讶地增强了体外T细胞增殖,并且在GvHD的发生率或严重程度方面没有产生临床益处。这与常规描述的MSC的免疫抑制活性形成对比。因此,这种用MSC处理的大鼠GvHD模型显示出在短期培养的常规MSC和克隆MSC之间淋巴细胞增殖和GvHD抑制的调节作用方面的有趣差异。
Mesenchymal stem cells (MSCs) derived from bone marrow are feasible for the exertion of a powerful immunoregulatory effect and thus shall hold a curative potency in T lymphocyte-dependent pathologies. This current article is intended to describe the method to investigate that MSCs might take advantage of regulation in graft-versus-host disease (GvHD), a major etiology of attack rate and lethality post allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were isolated from Lewis rat bone morrow and cultured for 4 weeks. The purification of enriched conventional MSCs and macrophages was achieved by autoMACS. Using the limiting dilution method, MSCs were cloned and then expanded until more than 6 months. The cultured MSCs showed a typical spindle-shaped morphology and immunophenotypes, lack of CD45 and CD11b/c expression. MSCs are also known for their ability to differentiate into adipocytes. MSCs, like macrophages, exhibit the immunomodulatory propensity to inhibit T lymphocyte proliferation. Following the adoptive transfer, MSCs regulate systemic Lewis to (Lewis x DA) F1 rat GvHD. Meanwhile, the cloned MSCs surprisingly enhanced T cell proliferation in vitro and yielded no clinical benefit in regard to the incidence or severity of GvHD. This is in contradistinction to the immunosuppressive activities of MSCs as conventionally described. Hence, this rat GvHD model treated with MSCs has shown intriguing differences in the regulatory effects of lymphocyte proliferation and GvHD repression between short-term cultured conventional MSCs and cloned MSCs.