Minireview: Complexity of Hematopoietic Stem Cell Regulation in the Bone Marrow Microenvironment

Abstract

Hematopoiesis in vertebrates is sustained over the duration of an organism's lifetime due to strict regulation of the highly hierarchical hematopoietic system, where a few immature hematopoietic stem cells (HSCs) continuously regenerate the entire blood supply, which is constantly being replaced. Although HSCs self-regulate through cell-autonomous processes, they also receive a variety of signals from their microenvironment or niche. Within the microenvironment, HSCs are regulated through both cell-cell interactions and secreted signals, including hormones. HSCs at the apex of the blood supply integrate these signals to produce progeny to support hematopoiesis while simultaneously maintaining a stem cell pool. In the past 10 years, advances in genetic models and flow cytometry have provided the tools to test how the microenvironment regulates HSCs. This review is organized in 3 main parts and will focus on cellular components of the HSC niche that are potential targets for hormonal signals, then review critical regulatory signals in the HSC niche, and finally highlight the emerging role of hormonal and paracrine signals in the bone marrow.

Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration

“…Previous work also revealed that dmPGE2-treated cells have increased levels of cyclic AMP, increased expression of CXCR4 and survivin, decreased apoptosis, and increased homing to the bone marrow stem cell niche (11, 14–16, 24, 25, 27). …”

“…The ability of PGE2 to promote hematopoiesis has been documented by two types of experiments: (i) ex vivo treatment of hematopoietic stem cells with dmPGE2 improves stem cell engraftment and consequent survival of mice, and (ii) administration of PGE2 or dmPGE2 to sub-lethally irradiated mice accelerates hematopoietic recovery and increases numbers of the short-term subtype of hematopoietic stem cells (11, 13–17, 24–27). Previous work also revealed that dmPGE2-treated cells have increased levels of cyclic AMP, increased expression of CXCR4 and survivin, decreased apoptosis, and increased homing to the bone marrow stem cell niche (11, 14–16, 24, 25, 27).…”

“…While bone marrow, colon, and liver each demonstrate very different tissue architectures, in each of these tissues this biological function of 15-PGDH is conserved, suggesting a biological generality of this pathway. PGE2 and dmPGE2 show activities that favor tissue regeneration when used to treat cells in culture and when administered to animals in pharmacological doses (11, 13–16, 18, 24–27). Our findings further imply that in normal in vivo physiology, prostaglandins play a widespread homeostatic role in the maintenance and repair of injury across multiple body tissues.…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…Niche maintenance is dependent on the complex interplay between soluble mediators, intrinsic signaling pathways and microenvironmental signals [62]. Regulation can be modulated by local signaling, by long-distance cues with hormones or by the autonomic nervous system.…”

Transglutaminase inhibition stimulates hematopoiesis and reduces aggressive behavior of crayfish, Pacifastacus leniusculus

“…The balance between self-renewal and differentiation of hematopoietic progenitor cells is tightly regulated by a variety of cells and signals, which include the microenvironment or niche (20). In crayfish, the progenitor cells are located in packed lobules or between lobules, which are surrounded by connective tissue and ECM (21).…”