The cellular composition and function of the bone marrow niche after allogeneic hematopoietic cell transplantation

Abstract

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.

Fig. 1. Composition and function of the bone marrow niche after HCT.

Schematic overview of the healthy bone marrow niche (a) and the bone marrow niche after hematopoietic cell transplantation (b). SCF Stem Cell Factor, CXCL12 C-X-C Motif Chemokine Ligand 12. VEGFR2 Vascular Growth Factor Receptor 1, TGF-β1 Transforming Growth Factor beta 1, ROS Reactive Oxygen Species, MSCs Mesenchymal Stromal Cells, ECs Endothelial Cells, HSCs Hematopoietic Stem Cells, IR irradiation.