The Dynamic Interface Between the Bone Marrow Vascular Niche and Hematopoietic Stem Cells in Myeloid Malignancy.

Laura Mosteo,Daniel H Wiseman,Emma J Searle,Joanna Storer,Kiran Batta,Delfim Duarte

doi:10.3389/fcell.2021.635189

Abstract

Hematopoietic stem cells interact with bone marrow niches, including highly specialized blood vessels. Recent studies have revealed the phenotypic and functional heterogeneity of bone marrow endothelial cells. This has facilitated the analysis of the vascular microenvironment in steady state and malignant hematopoiesis. In this review, we provide an overview of the bone marrow microenvironment, focusing on refined analyses of the marrow vascular compartment performed in mouse studies. We also discuss the emerging role of the vascular niche in “inflamm-aging” and clonal hematopoiesis, and how the endothelial microenvironment influences, supports and interacts with hematopoietic cells in acute myeloid leukemia and myelodysplastic syndromes, as exemplar states of malignant myelopoiesis. Finally, we provide an overview of strategies for modulating these bidirectional interactions to therapeutic effect in myeloid malignancies.

Highlights

Throughout an organism’s lifespan somatic stem cells face the substantial challenge of maintaining highly regenerative tissues, such as blood, that are characterized by rapid and continuous cell turnover
Mature blood cells are generated from hematopoietic stem cells (HSCs) in the complex and highly regulated process of hematopoiesis, which after early embryogenesis occurs predominantly within the bone marrow (BM)
We summarize advances made in the identification of BM microenvironmental components and their interactions with HSCs in health, physiological states and disease

Summary

Introduction

Throughout an organism’s lifespan somatic stem cells face the substantial challenge of maintaining highly regenerative tissues, such as blood, that are characterized by rapid and continuous cell turnover. EC-derived VEGF-C (another ligand for VEGFR2 that binds VEGFR3) is important for HSCs. Loss of EC-derived VEGF-C was reported to impair expression of key HSC-supporting factors both in ECs and in associated Lepr+ perivascular cells (described later), with these effects being dependent on VEGF-signaling regulation in ECs (Fang et al, 2020).

Results

Conclusion