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PMID: 15827136 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells.

Blood ·Vol. 106 ·No. 4 ·2005-08-15 ·Pages 1479-87

Liang Y, Van Zant G, Szilvassy SJ

Abstract

To test the hypothesis that aging has negative effects on stem-cell homing and engraftment, young or old C57BL/6 bone marrow (BM) cells were injected, using a limiting-dilution, competitive transplantation method, into old or young Ly5 congenic mice. Numbers of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) recovered from BM or spleen were measured and compared with the numbers initially transplanted. Although the frequency of marrow competitive repopulation units (CRUs) increased approximately 2-fold from 2 months to 2 years of age, the BM homing efficiency of old CRUs was approximately 3-fold lower than that of young CRUs. Surprisingly, the overall size of individual stem-cell clones generated in recipients receiving a single CRU was not affected by donor age. However, the increased ages of HSC donors and HSC transplant recipients caused marked skewing of the pattern of engraftment toward the myeloid lineage, indicating that HSC-intrinsic and HSC-extrinsic (microenvironmental) age-related changes favor myelopoiesis. This correlated with changes after transplantation in the rate of recovery of circulating leukocytes, erythrocytes, and platelets. Recovery of the latter was especially blunted in aged recipients. Collectively, these findings may have implications for clinical HSC transplantation in which older persons increasingly serve as donors for elderly patients.

MeSH Terms
Age Factors Animals Bone Marrow Cells Bone Marrow Transplantation Cell Count Cell Movement Graft Survival Hematopoiesis Hematopoietic Stem Cells/physiology Mice Mice, Inbred C57BL Mice, Inbred Strains Myelopoiesis Spleen/cytology
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Liang Ying
Department of Physiology, University of Kentucky, Lexington, KY, USA.
Van Zant Gary
Szilvassy Stephen J
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2004-11-4282
Published
2005-08-15
Epub
2005-00-12
Pages
1479-87
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895199
Subset
IM
Grants
NIA NIH HHS · AG16653 · United States
NIA NIH HHS · AG20917 · United States
NIA NIH HHS · AG24950 · United States
NHLBI NIH HHS · HL61392 · United States
External Links
PubMed source DOI: 10.1182/blood-2004-11-4282 PMC Full Text View journal details
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