Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology

• Published in: Leukemia Vol. 18; no. 3; pp. 575 - 583
• Main Authors: COLVIN, G. A, LAMBERT, J-F, ABEDI, M, HSIEH, C-C, CARLSON, J. E, STEWART, F. M, QUESENBERRY, P. J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.03.2004; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Blood Cell Count; Bone marrow; Bone Marrow Cells - cytology; Cell Separation - methods; Chimerism; Competition; Female; Graft Survival; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - cytology; Leukemia; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Progenitor cells; Spine; Stem cell transplantation; Stem cells; Syngeneic grafts; Transplants & implants; United States > US; Hematology; Stem cell; Determinant; Rodentia; total marrow cellularity; Cell biology; Hematopoietic cell; Homograft; Cell differentiation; bone marrow transplantation; Vertebrata; Mammalia; Mouse; Animal; Bone marrow; Graft; hematopoietic stem cells; Quantitative analysis
• DOI: 10.1038/sj.leu.2403268
• ISSN: 0887-6924

In unperturbed mice, the marrow cell numbers correlate with the stem cell numbers. High levels of long-term marrow engraftment are obtained with infusion of high levels of marrow cells in untreated mice. To address the issue of stem cell competition vs 'opening space', knowledge of total murine marrow cellularity and distribution of stem and progenitor cells are necessary. We determined these parameters in different mouse strains. Total cellularity in BALB/c mice was 530+/-20 million cells; stable from 8 weeks to 1 year of age. C57BL/6J mice had 466+/-48 million marrow cells. Using these data, theoretical models of infused marrow (40 million cells) replacing or adding to host marrow give chimerism values of 7.5 and 7.0%, respectively; the observed 8-week engraftment of 40 million male BALB/c marrow cells into female hosts (72 mice) gave a value of 6.91+/-0.4%. This indicates that syngeneic engraftment is determined by stem cell competition. Our studies demonstrate that most marrow cells, progenitors and engraftable stem cells are in the spine. There was increased concentration of progenitors in the spine. Total marrow harvest for stem cell purification and other experimental purposes was both mouse and cost efficient with over a four-fold decrease in animal use and a financial saving.