Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia.

Kevin Woods,Borhane Guezguez

doi:10.3389/fcell.2021.714716

Abstract

Mesenchymal stromal cells (MSCs) are a heterogenous cell population found in a wide range of tissues in the body, known for their nutrient-producing and immunomodulatory functions. In the bone marrow (BM), these MSCs are critical for the regulation of hematopoietic stem cells (HSC) that are responsible for daily blood production and functional immunity throughout an entire organism’s lifespan. Alongside other stromal cells, MSCs form a specialized microenvironment BM tissue called “niche” that tightly controls HSC self-renewal and differentiation. In addition, MSCs are crucial players in maintaining bone integrity and supply of hormonal nutrients due to their capacity to differentiate into osteoblasts and adipocytes which also contribute to cellular composition of the BM niche. However, MSCs are known to encompass a large heterogenous cell population that remains elusive and poorly defined. In this review, we focus on deciphering the BM-MSC biology through recent advances in single-cell identification of hierarchical subsets with distinct functionalities and transcriptional profiles. We also discuss the contribution of MSCs and their osteo-adipo progeny in modulating the complex direct cell-to-cell or indirect soluble factors-mediated interactions of the BM HSC niche during homeostasis, aging and myeloid malignancies. Lastly, we examine the therapeutic potential of MSCs for rejuvenation and anti-tumor remedy in clinical settings.

Highlights

Located within specific anatomical zones of the skeleton, the bone marrow (BM) is a specialized microenvironment or “niche” that lodges cells of hematopoietic and mesenchymal origins in various hierarchical committed states
The main role of the BM niche is the tight control of cell-fate decisions of the hematopoietic stem cells (HSCs) and their progeny to sustain the daily supply in functional blood and immune cells throughout life
Within the scope of this review, we refer to the nomenclature proposed by Matsuzaki et al (2014) and revised by Ambrosi et al (2019); according to which Mesenchymal Stromal Cell (MSC) are defined as bone marrow stromal cells bearing trilineage potential and expressing both Leptin receptor (LEPR) and PDGF-receptor α (PDGFR-α) in human and mouse

Summary

Introduction

Located within specific anatomical zones of the skeleton, the bone marrow (BM) is a specialized microenvironment or “niche” that lodges cells of hematopoietic and mesenchymal origins in various hierarchical committed states. In a recent scRNA-seq mapping experiment of large BM hematopoietic cell populations, a small amount of heterogeneous MSCs were captured, with one subset expressing high levels of the key bone marrow-homing cytokine CXCL12.

Results

Conclusion