Bone marrow localization and functional properties of human hematopoietic stem cells

PURPOSE OF REVIEW: Historically, studies of the hematopoietic stem cell (HSC) microenvironment in bone marrow have focused on the identification of individual supportive cell lineages likely to be responsible for maintaining HSCs in a self-renewing and regenerative state. More recently, awareness has developed regarding the broad and dynamic heterogeneity of nonhematopoietic cells that reside within the bone marrow space. We review recent insights that provide an emerging and complex context for understanding the spatially dependent regulation of HSC functional properties in the bone marrow and the collective inputs of multiple cell types. RECENT FINDINGS: Within the last 18 months, high-resolution imaging, xenograft modeling, and genetic mouse models have afforded innovative methods of detecting and interrogating HSCs with precision at the cellular level. Spatially distinct sites within the bone marrow house functionally divergent HSCs and progenitors, and these different habitats are becoming carefully characterized from a cellular and molecular perspective. This is critical toward understanding how bone marrow microenvironments adapt to accommodate cellular demands for hematopoiesis and how these mechanisms are disrupted in pathological conditions. SUMMARY: The bone marrow is not a continuum but an integrated unit with complex trophic interactions. Emphasis on human data will become necessary as these concepts mature and develop translationally toward changing clinical practices in HSC transplantation and even in the treatment of leukemias.