Analyzing hematopoietic stem cell homing, lodgment, and engraftment to better understand the bone marrow niche

Abstract

The existence of a bone marrow (BM) niche--the location in which hematopoietic stem cells (HSCs) reside--was proposed more than 30 years ago. Recent data suggest that the interaction of HSCs with cellular and extracellular components within the BM is critical for HSC regulation. The tracking of immunofluorescently labeled, prospectively isolated HSCs to and within the BM cavity allows the assessment of the regulatory processes involved in (1) homing, which involves transendothelial migration into the BM; (2) lodgment, including transmarrow migration through the extravascular space; and (3) BM reconstitution. Together, such analyses provide a better understanding of the cellular and extracellular components involved in the regulation of HSC quiescence and differentiation. Homing and lodgment of transplanted HSCs, the first critical steps in engraftment, involve multiple interactions between HSCs and the BM microenvironment. Herein, we describe a refined method of analyzing homing efficiency and spatial distribution of HSCs harvested from endosteal and/or central BM regions; we also review alternate methods. Using these techniques, microenvironment modifications within the recipient or surface protein-expression modifications on donor HSCs in animal models provide insights into components influencing the homing, lodgment, and engraftment processes.

Single and combined effect of retinoic acid and rapamycin modulate the generation, activity and homing potential of induced human regulatory T cells

“…Homing molecules to the intestine [104] and bone marrow [105] have been well characterized. Compelling evidence suggests that similarly as conventional naïve T cells, the migratory properties of FOXP3+ regulatory T cells are influenced by organ-specific dendritic cells and the tissue microenvironment [106].…”

Aging Effects on Cardiac Progenitor Cell Physiology

“…Thus, numerous physical and humoral signals coordinate HSC retention in the niches and movement from the niches to the peripheral circulation. The reverse process during which HSCs cross the endothelial wall and the extracellular matrix barriers is similarly controlled (46,132,186,188,189,264,268,290,299,332,342,343). Knowledge of the molecular pathways governing the migration of HSCs has been translated to the clinic; innovative protocols for the harvest of large numbers of HSCs and the optimization of their engraftment after systemic infusion have been developed to enhance the success of bone marrow transplantation (5,121,150,219,220,268,287).…”

Plasmacytoid dendritic cells in allogeneic hematopoietic cell transplantation: benefit or burden?

“…Like mobilization, HSC homing, localization and re-entry of donor hematopoietic progenitors back into the BM (engraftment) is dependent upon soluble factors like CXCL12/stromal cell-derived factor 1α and very late Ag 4 and cellular factors, 62 including Treg cells. 63 Along with Treg cells, a small CD8 + TCR − CD11b − CD11c + B220 + BM population in mice has been identified as engraftment facilitating cells (FCs).…”