Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czechia.
Front Immunol. 2024 Jun 14;15:1405210. doi: 10.3389/fimmu.2024.1405210. eCollection 2024.
In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.
在骨髓移植(BMT)中,造血重建细胞在清髓治疗后被引入,清髓治疗会消除现有的造血细胞并破坏造血组织内的基质。造血细胞和基质随后都经历再生。我们的研究比较了在清髓治疗后不久对小鼠进行第二次 BMT 与第一次 BMT 的结果,以及对经历初始移植后造血再生强劲的小鼠进行第二次 BMT 的结果。我们从植入效率、生成的血细胞类型和功能的持久性方面评估了第二次 BMT 的效果。我们的发现表明,再生的造血系统很容易容纳新移植的干细胞,包括那些具有强大生成 B 和 T 细胞能力的干细胞。重要的是,我们的研究发现了一个与血细胞生成恢复同时发生的有利于移植干细胞植入的窗口。重复 BMT 可以增强造血重建,并能够对经过基因修饰的自体干细胞进行治疗性给药。