Hematopoietic stem cell transplantation (HSCT) following myeloablative conditioning represents the only curative treatment option to overcome numerous hematologic malignancies. Despite the overall clinical success to achieve reconstitution of the blood system in many patients, the length of the aplastic phase until recovery response remains a critical parameter for patient survival. Fatal infections are the major risk factor for immunocompromised individuals and in many cases lead to transplant related morbidity and mortality. Therefore, we hypothesized that transplants from young donors might be beneficial for the spatiotemporal blood reconstitution in comparison to old grafts. Here we report on our multicolor-coded barcode system (BC32) to track hematopoietic stem and progenitor cell (HSPC) populations in a murine model of HSCT. By using different experimental settings of young and aged donor and recipient animals we compared the influence of age on graft composition, leukocyte recovery and more precisely, the contribution of individual HSPC subpopulations to the process. We show that blood reconstitution is substantially driven and maintained by HSCs and MPPs, while the latter accounted for higher output rates than HSCs, confirmed by FACS and NGS analyses. Reconstitution patterns were highly polyclonal and stable in all animals aside from variability between individual animals. This leads to the conclusion that HSPCs home, engraft and differentiate independently of donor and recipient age in our experimental conditions. Our findings add to ongoing efforts to expand the application of HSCT in older individuals while minimizing therapy related risks resulting from intensive myeloablative conditioning or incomplete blood reconstitution.

中文翻译：

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造血重建过程中造血干细胞和祖细胞群体的年龄独立影响

进行清髓治疗后进行造血干细胞移植（HSCT）是克服众多血液恶性肿瘤的唯一治疗选择。尽管在许多患者中获得了重建血液系统的整体临床成功，但再生障碍症直至恢复反应的时间仍然是患者生存的关键参数。致命感染是免疫功能低下个体的主要危险因素，在许多情况下会导致与移植相关的发病率和死亡率。因此，我们假设与旧移植相比，年轻捐赠者的移植可能对时空血液重建有益。在这里，我们报告了我们的多色编码条形码系统（BC32），以在HSCT小鼠模型中追踪造血干细胞和祖细胞（HSPC）种群。通过使用不同年龄和年龄的供体和受体动物的实验环境，我们比较了年龄对移植物组成，白细胞回收率的影响，更确切地说是对单个HSPC亚群对该过程的贡献。我们显示，血液重建在很大程度上由HSC和MPP驱动和维持，而FACS和NGS分析证实，后者比HSC的产出率更高。除了各个动物之间的变异性外，重组模式在所有动物中都是高度多克隆且稳定的。由此得出结论，在我们的实验条件下，HSPC可以独立于供体和受体的年龄回家，移入和分化。