Leung W, Ramírez M, Novelli E M, Civin C I
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-5001, USA.
J Investig Med. 1998 Aug;46(6):303-11.
Quantitative assays are needed to characterize the multilineage engraftment potential of clinical hematopoietic grafts. After we observed a dose-response relationship between the number of human hematopoietic cells transplanted into nonobese diabetic-scid/scid (NOD/SCID) mice and the number of human CD45+ cells recovered in the chimeras' marrows and spleens, we sought to develop a multiple linear regression model that allows quantitative comparisons of human cell engraftment in vivo.
We used this NOD/SCID xenotransplant model to compare the engraftment potential of cord blood vs. adult marrow or mobilized blood, after either of 2 commonly used clinical graft engineering procedures: CD34+ cell selection or T cell depletion.
The engraftment per transplanted cell was > 20 fold higher for cord blood cells, as compared to hematopoietic cells from adults. However, there was no difference in engraftment per CD34+ cell transplanted between marrow and mobilized blood. Levels of human cell engraftment from all sources could be increased by administration of human hematopoietic growth factors to human/mouse chimeras after transplantation. Correlation analysis of the number of human CD13+ myeloid cells and CD19+ B lymphoid cells in the chimeras' marrows 8 weeks after transplantation provided evidence that almost all the human myeloid and B lymphoid cells were derived from the same primitive precursor cells.
These findings and assay may be useful in the development of clinical hematopoietic cell therapies.
需要定量分析来描述临床造血移植物的多谱系植入潜力。在我们观察到移植到非肥胖糖尿病-重症联合免疫缺陷（NOD/SCID）小鼠体内的人造血细胞数量与嵌合体骨髓和脾脏中回收的人CD45+细胞数量之间存在剂量反应关系后，我们试图建立一个多元线性回归模型，以便对体内人细胞植入进行定量比较。
我们使用这种NOD/SCID异种移植模型，在两种常用的临床移植物工程程序（CD34+细胞选择或T细胞清除）中的任何一种之后，比较脐带血与成人骨髓或动员血的植入潜力。
与成人造血细胞相比，脐带血细胞每移植细胞的植入率高20倍以上。然而，骨髓和动员血之间每移植一个CD34+细胞的植入率没有差异。移植后向人/小鼠嵌合体施用人类造血生长因子可提高所有来源的人细胞植入水平。对移植后8周嵌合体骨髓中人类CD13+髓系细胞和CD19+B淋巴细胞数量的相关性分析提供了证据，表明几乎所有人类髓系和B淋巴细胞都来自同一原始前体细胞。
这些发现和分析方法可能对临床造血细胞治疗的发展有用。
