Nonhuman primate allogeneic hematopoietic stem cell transplantation by intraosseus vs intravenous injection: Engraftment, donor cell distribution, and mechanistic basis
Nonhuman primate allogeneic hematopoietic stem cell transplantation by intraosseus vs intravenous injection: Engraftment, donor cell distribution, and mechanistic basis
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DOI：
10.1016/j.exphem.2008.06.010
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发表时间：
2008-11-01
影响因子：
2.6
通讯作者：
Hwang, William Ying Khee
中科院分区：
文献类型：
--
作者：
Feng, Qi;Chow, Pierce K. H.;Hwang, William Ying Khee
Objective.造血干细胞移植（HSCT）的传统静脉（IV）给药途径可能导致供体细胞的放置效率低下，可能导致植入效果不佳和移植物抗宿主反应风险较高。为了在解剖学上与人相似的动物模型中进行移植和供体细胞分布的详细研究，我们在同种异体非人灵长类动物模型中进行了骨内（IO）和IV HSCT之间的首次直接归巢/移植效率比较，以评估IO递送后供体细胞归巢的效用和机制。将PKH 26膜染料标记的供体骨髓（BM）细胞移植到非清髓性条件非人灵长类动物。通过聚合酶链反应扩增供者特异性短串联重复序列位点证实嵌合体。与IO途径相比，IV输注在外周器官（包括肺、心脏、脾、肾和肝）中捕获的供体细胞多2.4至4.8倍。IO注射导致保留在注射部位BM中的供体细胞增加6.2倍，保留在远处BM部位的供体细胞增加2.7倍。选定的细胞粘附分子（CAM）的概况表明，IO HSCT后，更多的供体细胞表达CAM，可以促进BM归巢和重新分布到非注射侧BM腔。这种归巢效率的变化可能具有临床意义，因为与静脉输注相比，半相合受体的IO移植增强了供体细胞的植入。我们的研究结果表明，IO注射增强归巢和移植在非人灵长类动物HSCT。(c)2008 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. The traditional intravenous (IV) route of administration for hematopoietic stem cell transplantation (HSCT) may result in inefficient placement of donor cells, possibly contributing to suboptimal engraftment and higher risk of graft-vs-host reactions. In order to perform detailed studies of engraftment and donor cell distribution in an animal model with anatomical similarity to man, we performed the first direct homing/engraftment efficiency comparison between intraosseus (IO) and IV HSCT in allogeneic nonhuman primate animal model to assess the utility and mechanism of donor cell homing after IO delivery.Materials and Methods. Donor bone marrow (BM) cells labeled with PKH26 membrane dye were transplanted to nonmyeloablative-conditioned nonhuman primate animals. Chimerism was confirmed by polymerase chain reaction amplification of donor-specific short tandem repeat locus.Results. Compared to the IO route, IV infusion trapped 2.4- to 4.8-fold more donor cells in peripheral organs, including the lung, heart, spleen, kidney, and liver. IO injection resulting in a 6.2-fold increase in donor cells retained in the BM at the site of injection and a 2.7-fold increase in donor cells retained in distant BM sites. A profile of selected cell adhesion molecules (CAMs) demonstrated that after IO HSCT, more donor cells express CAMs that could facilitate BM homing and redistribution to non-injection-side BM cavities. This change in homing efficiency may be clinically significant because IO transplantation in haploidentical recipients enhanced donor cell engraftment when compared to IV delivery.Conclusion. Our results suggest that IO injection enhances both homing and engraftment in nonhuman primate HSCT. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.