Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Oncode Institute, Utrecht, The Netherlands.
Bone Marrow Transplant. 2022 Sep;57(9):1357-1364. doi: 10.1038/s41409-022-01728-0. Epub 2022 Jun 11.
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with a variety of malignant and non-malignant diseases. Despite its life-saving potential, HCT is associated with significant morbidity and mortality. Reciprocal interactions between hematopoietic stem cells (HSCs) and their surrounding bone marrow (BM) niche regulate HSC function during homeostatic hematopoiesis as well as regeneration. However, current pre-HCT conditioning regimens, which consist of high-dose chemotherapy and/or irradiation, cause substantial short- and long-term toxicity to the BM niche. This damage may negatively affect HSC function, impair hematopoietic regeneration after HCT and predispose to HCT-related morbidity and mortality. In this review, we summarize current knowledge on the cellular composition of the human BM niche after HCT. We describe how pre-HCT conditioning affects the cell types in the niche, including endothelial cells, mesenchymal stromal cells, osteoblasts, adipocytes, and neurons. Finally, we discuss therapeutic strategies to prevent or repair conditioning-induced niche damage, which may promote hematopoietic recovery and improve HCT outcome.
异基因造血细胞移植（HCT）是一种潜在的治愈疗法，适用于多种恶性和非恶性疾病的患者。尽管它具有挽救生命的潜力，但 HCT 与显著的发病率和死亡率相关。造血干细胞（HSCs）与其周围的骨髓（BM）龛之间的相互作用调节着 HSC 在稳态造血以及再生过程中的功能。然而，目前的 HCT 预处理方案包括高剂量化疗和/或放疗，会对 BM 龛造成严重的短期和长期毒性。这种损伤可能会对 HSC 功能产生负面影响，损害 HCT 后的造血再生，并导致与 HCT 相关的发病率和死亡率。在这篇综述中，我们总结了 HCT 后人类 BM 龛的细胞组成的现有知识。我们描述了 HCT 预处理如何影响龛中的细胞类型，包括内皮细胞、间充质基质细胞、成骨细胞、脂肪细胞和神经元。最后，我们讨论了预防或修复预处理诱导的龛损伤的治疗策略，这可能促进造血恢复并改善 HCT 结果。
