The bone marrow endosteal niche: how far from the surface?

Abstract

Hematopoietic stem cells (HSC) self-renewal takes place in the same microenvironment in which massive hematopoietic progenitor proliferation, commitment, and differentiation will occur. This is only made possible if the bone marrow microenvironment comprises different specific niches, composed by different stromal cells that work in harmony to regulate all the steps of the hematopoiesis cascade. Histological and functional assays indicated that HSC and multipotent progenitors preferentially colonize the endosteal and subendosteal regions, in close association with the bone surface. Conversely, committed progenitors and differentiated cells are distributed in the central and perisinusoidal regions, respectively. Over the last decade, many investigative teams sought to define which cell types regulate the HSC niche, how they are organized, and to what extent they interface with each other. System dynamics requires different stromal cells to operate distinct functions over similar HSC pools rather than a single stromal cell type controlling everything. Therefore, our focus herein is to depict the players in the endosteal and subendosteal regions, named the endosteal niche, a necessary step to better understand the interactions of the HSC within the niche and to identify potential targets to manipulate and/or modulate normal and malignant HSC behavior.

Keywords: BONE MARROW; ENDOSTEUM; HEMATOPOIETIC STEM CELLS; IN VIVO; NICHE; OSTEOBLAST.

Figure 1

Model of the bone marrow microenvironment subdivision as proposed by Lambertsen and Weiss [9] . Endosteal and subendosteal regions compose the endosteal niche, which harbors both the proliferative and quiescent HSC niches. This organization is easily adapted to the cavity of a long bone shaft, but a few anatomical arrangements must be considered when analyzing the bone marrow in the trabecular bone.

Figure 2

Schematic magnification of the endosteal and subendosteal regions, which compose the endosteal niche. At least, three different stromal cell types can be identified in the niche: A, osteoblasts; B, non-perivascular reticular cells, probably mostly pre-osteoblasts; C, perivascular reticular cells, probably mesenchymal stem cells. These cells will organize the HSC niche. Three interfaces must be considered: 1, osteoblast and perivascular cells; 2, perivascular cells and pre-osteoblasts; and 3, osteoblasts and pre-osteoblasts. Each stromal combination will create a distinct niche for the same HSC pool. How this is organized and what is the dynamic among them is still unknown.