Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in homing and engraftment

Abstract

Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche. Endothelial cells (ECs) are intimately associated with HSCs throughout the life of the stem cell, from the specialized endothelial cells that give rise to HSCs, to the perivascular niche endothelial cells that regulate HSC homeostasis. Recent studies have dissected the unique molecular and physical properties of the endothelial cells in the HSC vascular niche and their role in HSC biology, which may be manipulated to enhance hematopoietic stem cell transplantation therapies.

Bone marrow cell response after injury and during early stage of regeneration is independent of the tissue‐of‐injury in 2 injury models

“…The physical architecture of the BM was not disturbed in the skin/muscle injury despite the observed decrease in the levels of mature ECs. This indicates that mature ECs might also be key players in the reorganization of the BM upon injury, possibly involved in controlling the microvasculature network, the cellular traffic within the BM, and/or regulation of HSC niche (67). The response profiles of ECs and HSC were clustered together, further supporting that these 2 cellular populations are intimately related, with possible roles on HSC self-renewal and repopulation (31,68,69).…”

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

“…[45][46][47][48] While loss-offunction and in vitro studies have shown that CXCL12 promotes quiescence of HSCs, it has also been demonstrated that CXCL12 improves the homing of HSCs to the BM in a transplantation setting. 6,[49][50][51] The aim of this study was to test the effects of elevated Cxcl12 levels in vivo. To address this, we generated a transgenic mouse model that enables temporal and cell type-specific overexpression of CXCL12.…”

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

“…CXCL12 is produced by a variety of cells, including endothelial cells, perivascular cells and osteoblasts (Asada et al, 2017;Ding and Morrison, 2013;Ding et al, 2012;González et al, 2010;Mendelson and Frenette, 2014;Nagasawa et al, 1996;Pitt et al, 2015;Sugiyama et al, 2006). There is also evidence for sequestration of HSCs to the CXCL12-rich niche in the BM (Perlin et al, 2017;Reid et al, 2018;Sugiyama et al, 2006). Here, we observed that widespread overexpression of Cxcl12 hindered longterm engraftment and reconstitution of the various mature hematopoietic cells ( Figures 4C-D and S3C).…”

“…We and others have shown that vascular integrity is an important regulator of HSPC location and engraftment (Ding et al, 2012;Perlin et al, 2017;Poulos et al, 2017;Smith-Berdan et al, 2015. To determine if Cxcl12 overexpression causes vascular leak, we performed Miles assays by injecting Evans Blue dye in CXCL12+ or control mice ( Figure 4E).…”