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

Abstract

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.

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Acknowledgements

This work was supported by National Institutes of Health sponsored grants: P01 HL56920-03, P01 DK50222-03, R01 DK27424-18, R01 DK60084, R01 DK60090-01A1, and K08 DK64980-01.

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Correspondence to G A Colvin.

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Colvin, G., Lambert, JF., Abedi, M. et al. Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology. Leukemia 18, 575–583 (2004). https://doi.org/10.1038/sj.leu.2403268

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