Cited by 129Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchTelomeres, Telomerase, and Senescence

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Impaired Hematopoietic Stem Cell Functioning After Serial Transplantation and During Normal Aging

Kamminga, Leonie M., van Os, Ronald, Ausema, Albertina, Noach, Estelle J. K., Weersing, Ellen, Dontje, Bert, Vellenga, Edo, de Haan, Gerald·2005·STEM CELLS

DOI 10.1634/stemcells.2004-0066

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Abstract

Adult somatic stem cells possess extensive self-renewal capacity, as their primary role is to replenish aged and functionally impaired tissues. We have previously shown that the stem cell pool in short-lived DBA/2 (D2) mice is reduced during aging, in contrast to long-lived C57BL/6 (B6) mice. This suggests the existence of a genetically determined mitotic clock operating in stem cells, which possibly limits organismal aging. In the study reported here, unfractionated bone marrow (BM) cells or highly purified Lin(-)Sca-1(+)c-kit(+) (LSK) cells were serially transplanted in lethally irradiated D2 and B6 mice. In both strains, serial transplantation resulted in a substantial loss of stem cell activity. However, as we estimate that in B6 mice, the maximum number of population doublings of primitive cells is approximately 30, in D2 mice this is only approximately 20, resulting in a 1,000-fold difference in expansion potential, irrespective of whether whole bone marrow or purified hematopoietic stem cells (HSCs) were transplanted. Interestingly, recipients reconstituted with serially transplanted BM cells were able to accept a freshly isolated graft without any further conditioning. Finally, we show that whereas transplantation of BM cells into healthy, nonconditioned, young B6 recipients does not lead to engraftment, young BM cells do engraft and provide multilineage reconstitution in nonirradiated aged mice. Our data clearly establish the relevance of an intrinsic, genetically controlled program associated with impaired stem cell functioning during aging.

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Authors: Kamminga, L. M., van Os, R., Ausema, A., Noach, E. J. K., Weersing, E., Dontje, B., Vellenga, E., & de Haan, G.
Affiliations: University of Groningen (NL)
Department of Stem Cell Biology, University of Groningen, Groningen, The Netherlands
University Medical Center Groningen (NL)
ORCID: Kamminga, Leonie M.
Vellenga, Edo
Venue: STEM CELLS
Publisher: Oxford University Press (OUP)
Published: 2005-01
Volume: 23
Issue: 1
Pages: 82-92
ISSN: 1066-5099 (ISSN-L)
1549-4918
DOI: 10.1634/stemcells.2004-0066
OpenAlex: W2003077095
Cited by: 128
References: 56
Citations by year: 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 10 · 2019: 8 · 2018: 10 · 2017: 7 · 2016: 12 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 5
FWCI: 5.32
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
Locations: Stem Cells (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders: Ministry of Earth Sciences
Ministry of Education, India
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords: hematopoietic stem cells, aging, serial transplantation, stem cell self-renewal, bone marrow transplantation, LSK cells, DBA/2 mice, C57BL/6 mice, engraftment, multilineage reconstitution
MeSH terms: Animals, Cell Count, Evaluation Studies as Topic, Female, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Time Factors, Cellular Senescence, Hematopoietic Stem Cell Transplantation, Mice

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Impaired Hematopoietic Stem Cell Functioning After Serial Transplantation and During Normal Aging

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