Hematopoietic stem and progenitor cells and surrounding niche (HSPC niche)

The hematopoietic stem and progenitor cell (HSPC) niche is a complex, multi-component microenvironment primarily located in the bone marrow that governs the quiescence, self-renewal, and differentiation of HSPCs (Morrison & Scadden, 2014). It comprises various cellular elements, including mesenchymal stromal cells, osteoblasts, endothelial cells, and sympathetic neurons, which collectively provide the physical scaffolding and biochemical signals necessary for hematopoiesis (Crane et al., 2017). Key molecular interactions within this niche, such as the CXCL12-CXCR4 axis and the VLA-4-VCAM-1 interaction, are essential for anchoring HSPCs within their protective environment (Sugiyama et al., 2006). Dysregulation of the niche is implicated in various hematologic malignancies, where the "leukemic niche" can promote cancer cell survival and confer resistance to conventional therapies (Lane et al., 2009). Therapeutic interventions often target these interactions to mobilize HSPCs for bone marrow transplantation or to sensitize malignant cells to chemotherapy by displacing them from their protective surroundings (DiPersio et al., 2009). For instance, CXCR4 antagonists like plerixafor are used to disrupt the retention of HSPCs, facilitating their collection from the peripheral blood (Broxmeyer et al., 2005). Additionally, targeting adhesion molecules like E-selectin is being explored to improve outcomes in acute myeloid leukemia by forcing leukemic cells out of the niche (Winkler et al., 2012).

Other names

Bone marrow nicheHematopoietic microenvironmentHSPC microenvironmentStem cell nicheHematopoietic inductive microenvironment

Disruption of the CXCL12-CXCR4 signaling axis or inhibition of adhesion molecules (such as E-selectin or VLA-4) to mobilize hematopoietic stem cells or malignant cells from the bone marrow niche into the peripheral circulation.