A Quantitative Study of Bone Marrow Grafting: Implications for Human Bone Marrow Infusion

Pegg, D.E.

doi:10.1038/bjc.1962.46

Cited by 15 publications

(2 citation statements)

References 10 publications

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“…33 Flow cytometry and microscopy studies suggest that mitotic neutrophils in marrow account for 17% to 19% of total marrow cellularity. 2,34,35 The cellularity of bone marrow has been extensively studied in mice [36][37][38] and humans [39][40][41][42][43] ; the median of these different estimates is 13.05 3 10 9 cells per kilogram (supplemental Table 1). Taking a value of 17% for the marrow neutrophil precursor mitotic pool gives an estimate of 2. times.…”

Section: Resultsmentioning

confidence: 99%

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Lahoz-Beneytez

Elemans

Zhang

et al. 2016

Blood

228

234

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Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we developed a novel mechanistic model and applied it to previously published (n = 5) and newly generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (ratio = 0.26; from published values). Analysis of heavy water data sets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit time, were poorly defined. Analysis of glucose-labeling data yielded more precise estimates of half-life (0.79 ± 0.25 days; 19 hours) and marrow transit time (5.80 ± 0.42 days). Substitution of this marrow transit time in the heavy water analysis gave a better-defined blood half-life of 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing the ratio of blood neutrophils to mitotic neutrophil precursors (R) to vary yielded a best-fit value of 0.19. Reanalysis of the previously published model and data also revealed the origin of their long estimates for neutrophil half-life: an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than 1 day.

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Section: Resultsmentioning

confidence: 99%

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Lahoz-Beneytez

Elemans

Zhang

et al. 2016

Blood

228

234

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“…nucleated marrow cells. (6). In the second approach, total marrow elements are calculated on the basis of the mitotic index of the particular cell type related to the time of mitosis, assuming a steady state of production and no cell loss within compartments.…”

Section: Calculationsmentioning

confidence: 99%

Megakaryocyte quantitation

Harker¹

1968

J. Clin. Invest.

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A method is described for the quantitation of megakaryocytes. In this technic bone marrow sections obtained at the time of maximal marrow uptake of previously injected plasma bound 59Fe are counted for radioactivity as well as the number of megakaryocytes and nucleated red cells. We calculated the total megakaryocytes by relating the ratio of megakaryocyte: radioactivity with the total marrow 59Fe activity at the time of sampling. A multiple counting correction factor which is related to cell diameter and section thickness is required for quantitation of cell numbers from section material. The normal megakaryocyte number for the rat is 11.0 x 106/kg, and 6.1 x 106/kg for man.

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