Vrecenak Jesse D, Partridge Emily A, Pearson Erik G, Flake Alan W
Division of Pediatric Surgery, Washington University, St. Louis, Missouri.
Center for Fetal Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Biol Blood Marrow Transplant. 2020 Jan;26(1):e21-e24. doi: 10.1016/j.bbmt.2019.08.024. Epub 2019 Sep 5.
The rationale for in utero hematopoietic cell transplantation (IUHCT) rests on exploitation of normal events during hematopoietic and immunologic ontogeny to allow allogeneic hematopoietic engraftment without myeloablative conditioning. Host hematopoietic competition is among the primary barriers to engraftment in IUHCT. In the murine model this can be partially overcome by delivery of larger donor cell doses, but volume is limiting. Enrichment of donor hematopoietic stem cells (HSCs) would seem to offer a more efficient approach, but such enriched populations have engrafted poorly in existing models of IUHCT. To increase HSC dose while maintaining the presence of accessory cells, we used a less stringent enrichment protocol of single-step lineage depleted cells alone (lin-) or in combination with whole donor bone marrow mononuclear cells. Our results confirm that increasing doses of HSCs in combination with bone marrow accessory cells can dramatically improve engraftment after IUHCT. This represents a practical and clinically applicable strategy to maximize the engraftment potential of the donor graft without risk of treatment-associated toxicity.
宫内造血细胞移植（IUHCT）的基本原理基于对造血和免疫个体发育过程中正常事件的利用，从而在不进行清髓预处理的情况下实现异基因造血细胞植入。宿主造血竞争是IUHCT中细胞植入的主要障碍之一。在小鼠模型中，通过递送更大剂量的供体细胞可部分克服这一问题，但体积有限。富集供体造血干细胞（HSC）似乎提供了一种更有效的方法，但在现有的IUHCT模型中，此类富集群体的植入情况不佳。为了在维持辅助细胞存在的同时增加HSC剂量，我们采用了一种不太严格的富集方案，即单独使用单步去除谱系细胞（lin-）或与全供体骨髓单个核细胞联合使用。我们的结果证实，增加HSC剂量并结合骨髓辅助细胞可显著改善IUHCT后的植入情况。这代表了一种实用且临床适用的策略，可在无治疗相关毒性风险的情况下最大化供体移植物的植入潜力。
