The bone marrow pericyte: an orchestrator of vascular niche

Abstract

The concept of pericyte has been changing over years. This cell type was believed to possess only a function of trophic support to endothelial cells and to maintain vasculature stabilization. In the last years, the discovery of multipotent ability of perivascular populations led to the concept of vessel/wall niche. Likewise, several perivascular populations have been identified in animal and human bone marrow. In this review, we provide an overview on bone marrow perivascular population, their cross-talk with other niche components, relationship with bone marrow stromal stem cells, and similarities and differences with the perivascular population of the vessel/wall niche. Finally, we focus on the regenerative potential of these cells and the forthcoming challenges related to their use as cell therapy products.

Keywords: CD146; Nestin; bone marrow; endosteal niche; perivascular cell; vascular niche.

Figure 1.. Spatial organization of bone marrow niches.

Cartoon illustrating the organization of the vascular and endosteal niches and the distribution of the perivascular population. Periarteriolar cells are located atop the intima of the larger vessel and they secrete SCF and CXCL-12 factor in order to maintain HSCs in a quiescent state. Perisinusoidal cells are located around capillaries. They exert a regulation over proliferative HSCs ready to enter the blood stream through the fenestrated BM endothelium. HSCs located in the endosteal niche and around the adventitia of arterioles are less oxygenated and thus less exposed to ROS. This distribution creates an ROS gradient in which dormant HSC localize accordingly. BM: Bone marrow; HSC: Hematopoietic stem cell; ROS: Reactive oxygen species; SCF: Stem cell factor.

Figure 2.. Bone marrow perivascular cell multipotency.

Recapitulating scheme of multipotent ability demonstrated in vitro and/or in vitro by BM perivascular cells. CD146^- MSCs can acquire CD146 expression after exposure to normoxic condition. Similarly, in vitro cultured adventitial cell can phenotypically resemble microvascular pericyte. Perisinusoidal cells can differentiate in the classical tri-lineage of MSCs, although ability to commit to adipocyte fate is lost during in vitro expansion. Perisinusoidal cells can also acquire a VSMC-like phenotype after exposure to TGF-β, while a subset of CD146^- MSCs has the ability to shift toward a fibroblast-like appearance. Also disease condition as heart failure can push BM CD146⁺ to acquire a fibroblast-like phenotype. BM: Bone marrow; MSC: Mesenchymal stromal cell; RA: Retinoic acid; VSMC: Vascular smooth muscle cell.