Grant Matthew T, Nelvagal Hemanth Ramesh, Tecos Maria, Hamed Amal, Swanson Kerry, Cooper Jonathan D, Vrecenak Jesse D
Washington University in St. Louis School of Medicine, Department of Surgery, Division of Pediatric Surgery, St. Louis, MO, USA.
Washington University in St. Louis School of Medicine, Department of Pediatrics, Division of Genetics and Genomics, St. Louis, MO, USA.
Commun Biol. 2024 Dec 5;7(1):1624. doi: 10.1038/s42003-024-06847-6.
In utero hematopoietic cell transplantation (IUHCT) utilizes fetal immune tolerance to achieve durable chimerism without conditioning or immunosuppression during a unique window in fetal development. Though donor cells have been observed within the nervous system following in utero injection, the timeline and distribution of cellular trafficking across the blood-brain barrier following IUHCT is not well understood. We injected 20 × 10 adult bone marrow mononuclear cells intravenously at gestational age (GA) 12-17 days and found that donor cells were maximally concentrated in the brain with treatment between GA 13-14. Donor cell engraftment persisted within the brain at every timepoint analyzed and concentrated within the hindbrain with significantly more grafted cells than in the forebrain. Additionally, transplanted cells terminally differentiated into various nervous system cellular morphologies and also populated the enteric nervous system. This study is the first to document the timeline and distribution of donor cell trafficking into the immune-protected nervous system and serves as a foundation for the application of IUHCT to treat neurogenetic diseases.
宫内造血细胞移植（IUHCT）利用胎儿的免疫耐受性，在胎儿发育的一个独特窗口期内，无需预处理或免疫抑制即可实现持久的嵌合状态。尽管在宫内注射后已在神经系统中观察到供体细胞，但IUHCT后细胞穿越血脑屏障的时间线和分布情况尚不清楚。我们在妊娠12 - 17天静脉注射了20×10个成年骨髓单个核细胞，发现供体细胞在妊娠13 - 14周时治疗后在脑中的浓度最高。在分析的每个时间点，供体细胞在脑内持续植入，并集中在后脑，移植细胞明显多于前脑。此外，移植细胞最终分化为各种神经系统细胞形态，并在肠神经系统中定植。本研究首次记录了供体细胞进入免疫保护的神经系统的时间线和分布情况，为IUHCT治疗神经遗传性疾病的应用奠定了基础。
