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Numbers and functions of transplantable primitive immunohematopoietic stem cells. Effects of age.
Abstract
This report introduces a new method in immunology, a use of the binomial formula with covariance to estimate numbers and proliferative patterns of the most primitive lymphoid precursors. We studied the primitive stem cells (PSC) from which most circulating lymphocytes and erythrocytes were descended during 300 to 400 days in recipients of genetically distinguishable marrow mixtures in competitive repopulation. Equivalent PSC concentrations (Eq. PSC Conc. or Conc.) were estimated, with the notion of common PSCs contributing equally in lymphoid and myeloid compartments. Similar estimation was done for common PSCs from which lymphocytes (and erythrocytes) drawn at successive sampling times about 100 days apart were descended. The percentages of lymphocyte and erythrocyte types, P1 and Pe, measured in each recipient were closely correlated, especially after 6 months and later. Close correlations were also found in cells sampled at successive one hundred day intervals, especially after the first. Apparently a few PSCs or their direct descendents produced most of the blood lymphocytes and E, and this production continued for many months. Concentrations of these PSCs (Equivalent PSC concentrations) were about one per 105 marrow cells from young donors. This is much lower than previous estimates, probably because our methods focus only on the most interesting precursors, those from which most of the circulating cells were descended. Equivalent PSC concentrations were about two-fold higher in old donors; old marrow produced correspondingly higher P1 and Pe values, but these declined with time. There were also small increases with time in the P1 and Pe values with young donors. To explain the temporal trends, we suggest that excess concentrations of precursors less primitive than PSC are present in old marrow, and their contribution to the differentiated cell population gradually declines. Possibly such precursors, as well as true PSC, proliferate in old donors to compensate for deficiencies that develop with age.
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“HSCs exhibit multiple age-related changes that include impaired adherence to stromal cells and, in some strains of mice (15,16) and elderly humans (17), an increase in number.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [16]
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Metadata
- Authors
- Harrison, D. E., Astle, C. M., & Stone, M.
- Affiliations
- Jackson Laboratory (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1989-06-01
- Volume
- 142
- Issue
- 11
- Pages
- 3833-3840
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1509946101
- Cited by
- 148
- References
- 0
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 8 · 2012: 3
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institute on Aging (AG 06232, AG 00594)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK25687)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- competitive repopulation, bone marrow transplantation, erythroid precursors, stem cell proliferation, hematopoietic stem cell aging
- MeSH terms
- Aging, Animals, Bone Marrow, Cell Differentiation, Dose-Response Relationship, Immunologic, Erythrocyte Count, Erythrocytes, Female, Hematopoietic Stem Cells, Leukocyte Count, Lymphocytes, Male, Mice, Inbred C57BL, Bone Marrow Transplantation, Erythrocyte Transfusion, Lymphocyte Transfusion, Hematopoietic Stem Cell Transplantation, Mice
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