Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.
Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.
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DOI：
10.1016/j.stem.2011.02.003
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发表时间：
2011-04-08
期刊：
影响因子：
23.9
通讯作者：
North, Trista E.
中科院分区：
文献类型：
--
作者：
Goessling, Wolfram;Allen, Robyn S.;Guan, Xiao;Jin, Ping;Uchida, Naoya;Dovey, Michael;Harris, James M.;Metzger, Mark E.;Bonifacino, Aylin C.;Stroncek, David;Stegner, Joseph;Armant, Myriam;Schlaeger, Thorsten;Tisdale, John F.;Zon, Leonard I.;Donahue, Robert E.;North, Trista E.
造血干细胞（hsc）用于移植治疗以重建造血系统。当传统的造血干细胞来源无法获得时，人脐带血（hCB）移植已成为一种有吸引力的替代治疗选择，然而，移植的hCB造血干细胞的绝对数量明显低于骨髓或动员的外周血干细胞（MPBSCs）。我们之前证明了二甲基前列腺素E2 （dmPGE2）增加了脊椎动物模型中的hsc。在这里，我们描述了使用人类和非人类灵长类造血干细胞治疗dmpge2的治疗潜力的临床前分析。dmPGE2显著增加体外人造血集落形成总量，并增强异种移植后未分离和CD34+ hCB的植入。在非人灵长类动物自体移植中，dmpge2处理的CD34+ MPBSCs在输注后一年多的时间里表现出稳定的多系植入。总之，我们的分析表明，dmPGE2介导了人类和非人类灵长类动物造血干细胞的保守反应，并提供了足够的临床前信息，以支持进行fda批准的1期临床试验。
Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable, however, the absolute number of hCB HSCs transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2) increased HSCs in vertebrate models. Here, we describe preclinical analyses of the therapeutic potential of dmPGE2-treatment using human and non-human primate HSCs. dmPGE2 significantly increased total human hematopoietic colony formation in vitro and enhanced engraftment of unfractionated and CD34+ hCB following xenotransplantation. In non-human primate autologous transplantation, dmPGE2-treated CD34+ MPBSCs showed stable multilineage engraftment over one year post-infusion. Together, our analyses indicated that dmPGE2 mediates conserved responses in HSCs from human and non-human primates, and provided sufficient preclinical information to support proceeding to an FDA-approved phase 1 clinical trial.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
64.5
作者：
Goessling W;North TE;Loewer S;Lord AM;Lee S;Stoick-Cooper CL;Weidinger G;Puder M;Daley GQ;Moon RT;Zon LI
通讯作者：
Zon LI
影响因子：
4
作者：
Campbell, Timothy B.;Hangoc, Giao;Broxmeyer, Hal E.
通讯作者：
Broxmeyer, Hal E.
影响因子：
4.3
作者：
Ballen, Karen K.;Shpall, Elizabeth J.;Spitzer, Thomas R.
通讯作者：
Spitzer, Thomas R.
影响因子：
64.8
作者：
Gerber, HP;Malik, AK;Ferrara, N
通讯作者：
Ferrara, N