Open AccessHemopoietic Stem Cells with Higher Hemopoietic Potential Reside at the Bone Marrow Endosteum
Author(s) -
Haylock David N.,
Williams Brenda,
Johnston Hayley M.,
Liu Mira C.P.,
Rutherford Kate E.,
Whitty Genevieve A.,
Simmons Paul J.,
Bertoncello Ivan,
Nilsson Susan K.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0528
Subject(s) - haematopoiesis , bone marrow , biology , stem cell , immunology , hematopoietic stem cell , microbiology and biotechnology
It is now evident that hemopoietic stem cells (HSC) are located in close proximity to bone lining cells within the endosteum. Accordingly, it is unlikely that the traditional method for harvesting bone marrow (BM) from mice by simply flushing long bones would result in optimal recovery of HSC. With this in mind, we have developed improved methodologies based on sequential grinding and enzymatic digestion of murine bone tissue to harvest higher numbers of BM cells and HSC from the endosteal and central marrow regions. This methodology resulted in up to a sixfold greater recovery of primitive hemopoietic cells (lineage − Sca + Kit + [LSK] cells) and HSC as shown by transplant studies. HSC from different anatomical regions of the marrow exhibited important functional differences. Compared with their central marrow counterparts, HSC isolated from the endosteal region (a) had 1.8‐fold greater proliferative potential, (b) exhibited almost twofold greater ability to home to the BM following tail vein injection and to lodge in the endosteal region, and (c) demonstrated significantly greater long‐term hemopoietic reconstitution potential as shown using limiting dilution competitive transplant assays. Disclosure of potential conflicts of interest is found at the end of this article.