Cord-blood engraftment with ex vivo mesenchymal-cell coculture.
Cord-blood engraftment with ex vivo mesenchymal-cell coculture.
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DOI：
10.1056/nejmoa1207285
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发表时间：
2012-12-13
期刊：
影响因子：
--
通讯作者：
Shpall EJ
中科院分区：
文献类型：
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作者：
de Lima M;McNiece I;Robinson SN;Munsell M;Eapen M;Horowitz M;Alousi A;Saliba R;McMannis JD;Kaur I;Kebriaei P;Parmar S;Popat U;Hosing C;Champlin R;Bollard C;Molldrem JJ;Jones RB;Nieto Y;Andersson BS;Shah N;Oran B;Cooper LJ;Worth L;Qazilbash MH;Korbling M;Rondon G;Ciurea S;Bosque D;Maewal I;Simmons PJ;Shpall EJ
由于低细胞剂量导致的植入不良限制了脐带血移植的有效性。我们假设移植用间充质基质细胞体外扩增的脐带血可以改善移植效果。我们研究了31例接受2个脐带血单位移植的血液系统癌症成人的植入结果，其中1个单位含有在与同种异体间充质基质细胞共培养中体外扩增的脐带血。将这些患者的结果与80例接受2个单位未经处理的脐带血的历史对照进行比较。与间充质基质细胞共培养导致总有核细胞扩增的中位数因子为12.2，CD 34+细胞扩增的中位数因子为30.1。每移植1单位扩增和未处理的脐带血，患者接受的中位有核细胞总数为每千克体重8.34×107个，CD 34+细胞为每千克1.81×106个--比我们之前移植2单位未处理的脐带血的剂量高。在发生植入的患者中，接受扩增脐带血的患者中性粒细胞植入的中位时间为15天，而仅接受未经处理脐带血的对照组为24天（P<0.001）;血小板植入的中位时间分别为42天和49天（P = 0.03）。在第26天，有扩增的中性粒细胞植入的累积发生率为88%，而无扩增的为53%（P<0.001）;在第60天，血小板植入的累积发生率分别为71%和31%（P<0.001）。骨髓间充质干细胞扩增的脐带血细胞移植是安全有效的。与仅使用未经处理的脐带血相比，扩增的脐带血与未经处理的脐带血组合显著提高了植入。（由国家癌症研究所和其他机构资助; ClinicalTrials.gov编号，NCT 00498316。
Poor engraftment due to low cell doses restricts the usefulness of umbilical-cord-blood transplantation. We hypothesized that engraftment would be improved by transplanting cord blood that was expanded ex vivo with mesenchymal stromal cells. We studied engraftment results in 31 adults with hematologic cancers who received transplants of 2 cord-blood units, 1 of which contained cord blood that was expanded ex vivo in cocultures with allogeneic mesenchymal stromal cells. The results in these patients were compared with those in 80 historical controls who received 2 units of unmanipulated cord blood. Coculture with mesenchymal stromal cells led to an expansion of total nucleated cells by a median factor of 12.2 and of CD34+ cells by a median factor of 30.1. With transplantation of 1 unit each of expanded and unmanipulated cord blood, patients received a median of 8.34×107 total nucleated cells per kilogram of body weight and 1.81×106 CD34+ cells per kilogram — doses higher than in our previous transplantations of 2 units of unmanipulated cord blood. In patients in whom engraftment occurred, the median time to neutrophil engraftment was 15 days in the recipients of expanded cord blood, as compared with 24 days in controls who received unmanipulated cord blood only (P<0.001); the median time to platelet engraftment was 42 days and 49 days, respectively (P = 0.03). On day 26, the cumulative incidence of neutrophil engraftment was 88% with expansion versus 53% without expansion (P<0.001); on day 60, the cumulative incidence of platelet engraftment was 71% and 31%, respectively (P<0.001). Transplantation of cord-blood cells expanded with mesenchymal stromal cells appeared to be safe and effective. Expanded cord blood in combination with unmanipulated cord blood significantly improved engraftment, as compared with unmanipulated cord blood only. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00498316.)