Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease

Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease
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DOI:
10.1111/j.1365-2141.2008.07040.x
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发表时间:
2008-04-01
影响因子:
6.5
通讯作者:
Flake, Alan W.
Flake, Alan W.
中科院分区:
医学2区
文献类型:
--
作者:
Badillo, Andrea T.;Peranteau, William H.;Flake, Alan W.

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人类和小鼠基质祖细胞(SPCs)在体外可抑制同种异体反应,提示SPCs可能在预防或治疗移植物抗宿主病(GVHD)方面具有临床应用价值。然而,体内研究的结果是相互矛盾的。本研究利用建立的小鼠急性GVHD模型来评估骨髓源性小鼠SPCs (mSPCs)预防或治疗GVHD的能力。通过将B6骨髓和脾脏细胞移植到致命照射(900 cGy) B6 x BALB/c F-1受体中建立GVHD。mSPCs使用不同的剂量和时间方案来预防或治疗GVHD。移植后,每天监测小鼠的体重和存活率。使用临床GVHD评分系统比较症状严重程度的差异。所有GVHD对照组小鼠均死于致死性GVHD。与对照组相比,接受mSPCs预防GVHD治疗的所有组继续发展为临床GVHD,病程或严重程度没有改变。GVHD发生后给予mSPC治疗未能改善病程。我们得出结论,在这个模型中,SPCs在体外抑制同种异体反应的能力与体内预防或治疗急性GVHD无关。
Human and murine stromal progenitor cells (SPCs) can suppress alloresponse in vitro, suggesting that SPCs may have clinical application toward prevention or treatment of graft-versus-host disease (GVHD). However, th eresults of in vivo studies have been conflicting. This study utilized an established murine model of acute GVHD to assess the ability of bone marrow derived murine SPCs (mSPCs) to prevent or treat GVHD. GVHD was established by transplantation of B6 bone marrow and spleen cells into lethally irradiated (900 cGy) B6 x BALB/c F-1 recipients. mSPCs were administered using various dose and timing protocols designed to either prevent or treat GVHD. After transplantation, mice were monitored daily for weight and survival. Differences in symptom severity were compared using a clinical GVHD scoring system. All GVHD control mice died of lethal GVHD. All groups treated with mSPCs for the prevention of GVHD went on to develop clinical GVHD with no alteration of the disease course or severity compared to controls. Administration of mSPC after the development of GVHD failed to improve the disease course. We conclude that in this model, the ability of SPCs to suppress alloresponse in vitro does not correlate with in vivo prevention or treatment of acute GVHD.