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. 1982 Aug;70(2):242–253. doi: 10.1172/JCI110611

Hematopoietic Stem Cells with High Proliferative Potential

ASSAY OF THEIR CONCENTRATION IN MARROW BY THE FREQUENCY AND DURATION OF CURE OF W/Wv MICE

Dane R Boggs 1,2,3, Sallie S Boggs 1,2,3, Debra F Saxe 1,2,3, Lora A Gress 1,2,3, Don R Canfield 1,2,3
PMCID: PMC371230  PMID: 6124553

Abstract

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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