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Changes in the frequencies of human hematopoietic stem and progenitor cells with age and site

Authors
  • Farrell, Tracy L.
  • McGuire, Timothy R.
  • Bilek, Laura D.
  • Brusnahan, Susan K.
  • Jackson, John D.
  • Lane, Judy T.
  • Garvin, Kevin L.
  • O’Kane, Barbara J.
  • Berger, Ann M.
  • Tuljapurkar, Sonal R.
  • Kessinger, M. Anne
  • Sharp, John Graham1, 2, 3, 2, 4, 2, 5, 2, 6, 7, 8, 2, 9, 2, 10, 11, 12, 13, 2, 14, 2
  • 1 Department of Genetics, Cell Biology and Anatomy
  • 2 University of Nebraska Medical Center
  • 3 Pharmacy Practice
  • 4 School of Allied Health Professions
  • 5 Pharmaceutical Sciences
  • 6 Institute for Regenerative Medicine
  • 7 Wake Forest University
  • 8 Pulmonary, Critical Care and Sleep Medicine
  • 9 Orthopaedic Surgery and Rehabilitation
  • 10 School of Dentistry
  • 11 Creighton University
  • 12 Adult Health and Illness
  • 13 College of Nursing
  • 14 Internal Medicine Oncology/Hematology
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Nov 06, 2013
Volume
42
Issue
2
Pages
146–154
Identifiers
DOI: 10.1016/j.exphem.2013.11.003
Source
Elsevier
License
Unknown

Abstract

This study enumerated CD45hi/CD34+ and CD45hi/CD133+ human hematopoietic stem cells (HSCs) and progenitor granulocyte-macrophage colony forming cells (GM-CFCs) in blood and trochanteric and femoral bone marrow in 233 individuals. Stem cell frequencies were determined with multiparameter flow cytometry and using an internal control to determine the intrinsic variance of the assays. Progenitor cell frequency was determined using a standard colony assay technique. The frequency of outliers from undetermined methodological causes was highest for blood, but less than 5% for all values. The frequency of CD45hi/CD133+ cells correlated highly with the frequency of CD45hi/CD34+ cells in trochanteric and femoral bone marrow. The frequency of these HSC populations in trochanteric and femoral bone marrow rose significantly with age. In contrast, there was no significant trend of either of these cell populations with age in the blood. Trochanteric marrow progenitor GM-CFCs showed no significant trends with age, but femoral marrow GM-CFCs trended downward with age, potentially because of the reported conversion of red marrow at this site to fat with age. Hematopoietic stem and progenitor cells exhibited changes in frequencies with age that differed between blood and bone marrow. We previously reported that side population (SP) multipotential HSC, which includes the precursors of CD45hi/CD133+ and CD45hi/CD34+, decline with age. Potentially the increases in stem cell frequencies in the intermediate compartment between SP and GM progenitor cells observed in this study represent a compensatory increase for the loss of more potent members of the HSC hierarchy.

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