Regulation of hematopoiesis in endosteal microenvironments

Abstract

After birth, the hematopoietic system develops along with bone formation in mammals. Osteolineage cells are derived from mesenchymal progenitor cells, and differentiate into several types of bone-forming cells. Of the various types of cell constituents in bone marrow, osteolineage cells have been shown to play important roles in hematopoiesis. Early studies have identified osteoblasts as a hematopoietic stem cell niche component. Since that time, the role of endosteal microenvironment as a critical regulator of hematopoietic stem/progenitor cell (HSC/ HPC) behavior has been appreciated particularly under stress conditions, such as cytokine-induced HSC/HPC mobilization, homing/engraftment after bone marrow transplantation, and disease models of leukemia/myelodysplasia. Recent studies revealed that the most differentiated osteolineage cells, i.e., osteocytes, play important roles in the regulation of hematopoiesis. In this review, we provide an overview of recent advances in knowledge of regulatory hematopoietic mechanisms in the endosteal area.

High plasma osteocalcin is associated with low blood haemoglobin in elderly men: the MrOS Sweden Study

“…The adult human bone marrow (BM) contains, in addition to haematopoietic stem cells (HSCs), mesenchymal stem cells which differentiate into a variety of mesenchymal cells including osteoblasts, osteocytes, adipocytes, myocytes and chondrocytes. There is growing evidence of a functional relationship between bone metabolism and haematopoiesis, suggesting that osteoblasts are involved in the regulation of haematopoiesis in both normal and abnormal states . Haematopoiesis is regulated by multiple growth factors, hormones and cytokines present in the BM as well as in peripheral blood.…”

“…However, the locations and mixture of subpopulations of HSCs are still not fully known; indeed, there may be distinct niches for different subpopulations. Several lines of evidence suggest, however, that osteolineage cells play an important role in haematopoiesis by regulating this specific local microenvironment, although the molecular mechanisms are not completely understood.…”

Navigating the bone marrow niche: translational insights and cancer-driven dysfunction

“…22 These cells are in close proximity to HSCs; moreover, regulatory factors that enhance MSC differentiation into the osteoblastic lineage can also promote the development of the bone marrow niche as well as the expansion and egress of HSCs. 23 The Kronenberg group was one of the first to establish the importance of osteoblasts in maintaining HSCs within the niche.…”

Eltrombopag after allogeneic haematopoietic cell transplantation in a case of poor graft function and systematic review of the literature

“…Poor graft function or late graft failure after allogeneic transplantation can result from failed engraftment of long‐term engrafting cells. Damage to stem cell niches in the marrow microenvironment or a paucity of long‐term HSCs in allogeneic grafts may contribute to failed engraftment in this setting (Asada & Katayama, ). The development of strategies to expand HSCs ex vivo prior to transplantation has been considered for cord blood transplantation to augment the engrafting potential of limiting doses of HSCs (Pineault & Abu‐Khader, ).…”