Superior survival of ex vivo cultured human reticulocytes following transfusion into mice
Superior survival of ex vivo cultured human reticulocytes following transfusion into mice
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DOI：
10.3324/haematol.2016.154443
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发表时间：
2017-03-01
期刊：
影响因子：
10.1
通讯作者：
Blair, Allison
中科院分区：
文献类型：
--
作者：
Kupzig, Sabine;Parsons, Stephen F.;Blair, Allison
从干细胞来源产生培养的红细胞可以满足输血依赖患者的未满足的临床需求，特别是在缺乏足够和安全血液供应的国家。通过离体扩增从成人外周血或脐带血的人CD 34（+）细胞产生培养的红细胞，并与标准红细胞浓缩物进行全面的体内存活比较。使用来自脐带血和外周血的CD 34（+）细胞实现显著扩增（> 10（5）倍），产生高产量的去核培养红细胞。输血后，与标准成人红细胞相比，在小鼠循环中可检测到更高水平的培养红细胞。来自脐带血或外周血来源的培养血细胞的比例在输血后24小时仍然很高（分别为82 +/- 5%和78 +/-9%），而标准成人血细胞迅速下降到此时仅为49 +/- 9%。此外，小鼠培养血细胞的存活时间比标准成人红细胞的存活时间长。培养的血细胞和来自同一供体的标准成人红细胞的配对比较证实了培养细胞的增强的体内存活能力。本文的研究首次证明，使用更接近模拟临床输血的体内模型，离体产生的培养红细胞比供体红细胞存活更长时间。培养的红细胞可以通过减少所需的输血次数为输血依赖患者提供优势。
The generation of cultured red blood cells from stem cell sources may fill an unmet clinical need for transfusion-dependent patients, particularly in countries that lack a sufficient and safe blood supply. Cultured red blood cells were generated from human CD34(+) cells from adult peripheral blood or cord blood by ex vivo expansion, and a comprehensive in vivo survival comparison with standard red cell concentrates was undertaken. Significant amplification (> 10(5)-fold) was achieved using CD34(+) cells from both cord blood and peripheral blood, generating high yields of enucleated cultured red blood cells. Following transfusion, higher levels of cultured red cells could be detected in the murine circulation compared to standard adult red cells. The proportions of cultured blood cells from cord or peripheral blood sources remained high 24 hours post-transfusion (82 +/- 5% and 78 +/- 9%, respectively), while standard adult blood cells declined rapidly to only 49 +/- 9% by this time. In addition, the survival time of cultured blood cells in mice was longer than that of standard adult red cells. A paired comparison of cultured blood cells and standard adult red blood cells from the same donor confirmed the enhanced in vivo survival capacity of the cultured cells. The study herein represents the first demonstration that ex vivo generated cultured red blood cells survive longer than donor red cells using an in vivo model that more closely mimics clinical transfusion. Cultured red blood cells may offer advantages for transfusion-dependent patients by reducing the number of transfusions required.