Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure
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Long-term functional capacities of marrow cell lines were defined by competitive repopulation, a technique capable of detecting a small decline in repopulating abilities. There was little or no difference between cells from old and young donors, but a single serial transplantation caused a large decline in repopulating ability. Varying the numbers of marrow cells transplanted into the initial carrier from 10(5) to 10(7) did not alter the ability of the carrier's marrow cells to repopulate in competition with previously untransplanted cells. This ability was improved only in carriers that had received 10(8) marrow cells, although deleterious effects of transplantation were still present. These effects were not solely caused by cell damage from the transplantation procedure, because transplantation by parabiosis, or recovery from sublethal irradiation without transplantation, reduced repopulating abilities as much as transplanting 10(5) to 10(7) marrow cells. The transplantation effect also was not caused solely by irradiation, because the same effect appeared in unirradiated W/Wv carriers. The transplantation effect was more pronounced when donors were identified by hemoglobin type than by chromosome markers, implying that nonerythroid cell lines may be less affected by transplantation than erythroid precursor cells. When the effects of a lifetime of normal function and a single transplantation were compared, the latter caused 3-7 times more decline in repopulating abilities of phytohemagglutinin-responsive cell precursors, and at least 10-20 times more decline in erythroid cell precursors. Stem cell lines can be serially transplanted at least five times before losing their ability to repopulate and save lethally irradiated recipients or to cure genetically anemic mice. Therefore, if transplantation causes an acceleration of the normal aging process, these figures suggest that stem cells should be able to function normally through at least 15-50 life spans.
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Aged HSCs transplanted into young mice are functionally worse than young HSCs.
“That aged HSC are functionally impaired compared with their young counterparts upon transplantation in young mice”
From Aging of hematopoietic stem cells (2018) · cites this paper as [5]
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Self-citation
- Authors
- Harrison, D. E., & Astle, C. M.
- Affiliations
- Jackson Laboratory (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1982-12-01
- Volume
- 156
- Issue
- 6
- Pages
- 1767-1779
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2186863
- OpenAlex
- W2097857054
- Cited by
- 281
- References
- 39
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- hematopoietic stem cells, competitive repopulation, serial transplantation, donor age, parabiosis, sublethal irradiation, erythroid precursors, stem cell aging, bone marrow transplantation, hemoglobin types
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Cell Count, Erythropoiesis, Female, Hematopoietic Stem Cells, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Parabiosis, Transplantation, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation, Mice
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