The Intravenous Route of Injection Optimizes Engraftment and Survival in the Murine Model of In Utero Hematopoietic Cell Transplantation
The Intravenous Route of Injection Optimizes Engraftment and Survival in the Murine Model of In Utero Hematopoietic Cell Transplantation
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DOI：
10.1016/j.bbmt.2016.01.017
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发表时间：
2016-06-01
影响因子：
4.3
通讯作者：
Peranteau, William H.
中科院分区：
文献类型：
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作者：
Boelig, Matthew M.;Kim, Aimee G.;Peranteau, William H.
宫内造血细胞移植(IUHCT)具有治疗多种先天性血液病的潜力。供体植入水平低限制了临床应用。优化供体细胞输送到胎儿肝脏(FL)的技术有可能提高IUHCT的植入率和临床成功率。我们比较了3种临床适用的注射途径(静脉注射、腹腔注射和肝内注射)。并在IUHCT小鼠模型中评估了短期和长期供体细胞植入和胎儿存活率。我们假设静脉注射。途径将促进供体细胞直接归巢到FL，从而增加植入，并允许更大的注射量而不会增加胎儿死亡率。我们证明了静脉注射。结果显示：(1)移植后FL的供体细胞数量迅速扩散，而移植后的移植延迟扩散。和I.H.(2)在产前早期时间点进行更高的FL和脾移植；(3)增强稳定的长期外周血细胞移植；(4)提高输液量时的存活率，从而实现更高的供体细胞剂量和更长的长期移植。这些发现支持静脉注射的使用。IUHCT的临床方案路线。(C)2016年美国血液和骨髓移植学会。
In utero hematopoietic cell transplantation (IUHCT) has the potential to treat a number of congenital hematologic disorders. Clinical application is limited by low levels of donor engraftment. Techniques that optimize donor cell delivery to the fetal liver (FL), the hematopoietic organ at the time of IUHCT, have the potential to enhance engraftment and the clinical success of IUHCT. We compared the 3 clinically applicable routes of injection (intravenous [i.v.], intraperitoneal [i.p.], and intrahepatic [i.h.]) and assessed short- and long-term donor cell engraftment and fetal survival in the murine model of IUHCT. We hypothesized that the i.v. route would promote direct donor cell homing to the FL, resulting in increased engraftment and allowing for larger injectate volumes without increased fetal mortality. We demonstrate that the i.v. route results in (1) rapid diffuse donor cell population of the FL compared with delayed diffuse engraftment after the i.p. and i.h. routes; (2) higher FL and spleen engraftment at early prenatal time points; (3) enhanced stable long-term peripheral blood donor cell engraftment; and (4) improved survival at higher injectate volumes, allowing for higher donor cell doses and increased long-term engraftment. These findings support the use of an i.v. route for clinical protocols of IUHCT. (C) 2016 American Society for Blood and Marrow Transplantation.