Changes in the frequencies of human hematopoietic stem and progenitor cells with age and site.
This study enumerated CD45(hi)/CD34(+) and CD45(hi)/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 CD45(hi)/CD133(+) cells correlated highly with the frequency of CD45(hi)/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 CD45(hi)/CD133(+) and CD45(hi)/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.
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Tracy L
TL
Farrell
Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, USA.
Timothy R
TR
McGuire
School of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE, USA.
Laura D
LD
Bilek
Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Susan K
SK
Brusnahan
Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA.
John D
JD
Jackson
Pulmonary, Critical Care and Sleep Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Judy T
JT
Lane
Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA.
Kevin L
KL
Garvin
School of Dentistry, Creighton University, Omaha, NE, USA.
Barbara J
BJ
O'Kane
Adult Health and Illness, College of Nursing, University of Nebraska Medical Center, Omaha, NE, USA.
Ann M
AM
Berger
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Sonal R
SR
Tuljapurkar
Internal Medicine Oncology/Hematology, University of Nebraska Medical Center, Omaha, NE, USA.
M Anne
MA
Kessinger
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: jsharp@unmc.edu.
John Graham
JG
Sharp
D000375:Aging / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans
D015703:Antigens, CD