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Analyzing hematopoietic stem cell homing, lodgment, and engraftment to better understand the bone marrow niche
Author(s) -
Heazlewood Shen Y.,
Oteiza Ana,
Cao Huimin,
Nilsson Susan K.
Publication year - 2014
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12329
Subject(s) - homing (biology) , haematopoiesis , stem cell , bone marrow , microbiology and biotechnology , biology , hematopoietic stem cell , niche , immunology , ecology
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.