Hematopoietic Stem Cells with High Proliferative Potential: ASSAY OF THEIR CONCENTRATION IN MARROW BY THE FREQUENCY AND DURATION OF CURE OF W/Wv MICE (original) (raw)
Free access | 10.1172/JCI110611
Sallie S. Boggs, Debra F. Saxe, Lora A. Gress, and Don R. Canfield
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Graduate School of Public Health, Pittsburgh, Pennsylvania 15261
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Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Graduate School of Public Health, Pittsburgh, Pennsylvania 15261
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Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Graduate School of Public Health, Pittsburgh, Pennsylvania 15261
Find articles by Saxe, D. in:[JCI](/search/results?q=author.first%5Fname%3A%22Debra F.%22+author.last%5Fname%3A%22Saxe%22&search%5Ftype=advanced) |PubMed |Google Scholar
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Graduate School of Public Health, Pittsburgh, Pennsylvania 15261
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Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261
Graduate School of Public Health, Pittsburgh, Pennsylvania 15261
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Published August 1, 1982 -More info
Published August 1, 1982 -Version history
This study was designed to approach two primary questions concerning hematopoietic stem cells (HSC) in mice: what is the concentration of HSC with extensive proliferative potential in marrow, and how long can an HSC continue to function in an intact animal? The assay system was the W/Wv mouse, a mouse with an inherited HSC defect, reflected in a reduction in all myeloid tissue and most particularly in a macrocytic anemia.
A single chromosomally marked HSC will reconstitute the defective hematopoietic system of the W/Wv. The concentration of HSC in normal littermate (+/+) marrow was assayed by limiting dilution calculation using cure of W/Wv as an end point (correction of anemia and erythrocytes' macrocytosis) and found to be ∼10/105. This is significantly less than spleen colony forming cell (CFU-S) concentration: ∼220/105 in +/+ and ranging from 50 to 270/105 in various other studies. Blood values were studied at selected intervals for as long as 26 mo. Of 24 initially cured mice, which were observed for at least 2 yr, 75% remained cured. However, of all cured mice, 17 lost the cure, returning to a macrocytic anemic state. Cured mice had normal numbers of nucleated and granulocytic cells per humerus and a normal concentration of CFU-S. However, cure of secondary W/Wv recipients by this marrow was inefficient compared with the original +/+ marrow. These studies suggest the CFU-S assay over-estimates extensively proliferating HSC or perhaps does not assay such a cell. A single such HSC can not only cure a W/Wv, but can sustain the cure for 2 yr or more, despite a relative deficit of cells capable of curing other W/Wv. However, the duration of sustained cure may be finite.
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