犬类子宫内造血干细胞移植：探索最大程度提高植入率的胎龄窗口机会。

In utero hematopoietic stem cell transplantation in canines: exploring the gestational age window of opportunity to maximize engraftment.

机构信息

Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Walter Reed National Military Medical Center, Bethesda, Md 20889, USA. scott.petersen @med.navy.mil

出版信息

Fetal Diagn Ther. 2013;33(2):116-21. doi: 10.1159/000346211. Epub 2013 Jan 19.

DOI:10.1159/000346211

PMID:23343577

Abstract

OBJECTIVE

In utero hematopoietic stem cell transplantation (IUHSCT) is a promising therapy for a variety of congenital disorders. Our objective was to determine the optimal time in gestation for IUHSCT in a canine model.

METHODS

IUHSCT was performed in day 31-50 (term 63) fetal canines with CD34+ cells isolated from paternal bone marrow at doses of 0.09-3.4 × 10⁹ CD34+ cells/kg and T cells (CD3+/CD5+) from paternal blood at 0.11-1.1 × 10⁹ cells/kg. Engraftment was assayed using PCR-based chimerism analysis (SRY gene detection for female recipients, and unique microsatellite loci for both sexes).

RESULTS

Microchimerism and chimerism were present in multiple recipients across most gestational ages at transplant. Maximal engraftment was obtained in hematopoietic tissues in transplants performed at 42 days. At extremes of recipient gestational age, minimal to no engraftment was seen.

CONCLUSION

Fetal age at the time of IUHSCT plays an important role in achieving engraftment in our canine model.

摘要

目的

子宫内造血干细胞移植（IUHSCT）是治疗多种先天性疾病的一种有前途的疗法。我们的目的是确定犬模型中 IUHSCT 的最佳妊娠时间。

方法

在妊娠第 31-50 天（胎龄 63）的胎儿犬中进行 IUHSCT，从父系骨髓中分离出 CD34+细胞，剂量为 0.09-3.4×10⁹ CD34+细胞/kg，从父系血液中分离出 T 细胞（CD3+/CD5+），剂量为 0.11-1.1×10⁹细胞/kg。通过基于 PCR 的嵌合体分析（对雌性受者进行 SRY 基因检测，对两性均使用独特的微卫星位点）检测嵌合体。