Hematopoietic stem-cell behavior in nonhuman primates

Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated g...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2007-09, Vol.110 (6), p.1806-1813
Main Authors: Shepherd, Bryan E., Kiem, Hans-Peter, Lansdorp, Peter M., Dunbar, Cynthia E., Aubert, Geraldine, LaRochelle, Andre, Seggewiss, Ruth, Guttorp, Peter, Abkowitz, Janis L.
Format: Article
Language:English
Subjects:
Animals
Antigens, CD34 - metabolism
Biological and medical sciences
Cell Differentiation
Cell Proliferation
Computer Simulation
Genetic Markers
Genetic Vectors
Granulocytes - cytology
Granulocytes - physiology
Hematologic and hematopoietic diseases
Hematopoiesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - physiology
Macaca mulatta - genetics
Medical sciences
Papio - genetics
Retroviridae
Stochastic Processes
Telomere
Time Factors
Transduction, Genetic
Transgenes - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated gene transfer (N = 11 baboons; N = 7 rhesus macaques) and quantitation of the average telomere length of granulocytes (N = 132 baboons; N = 14 macaques), together with stochastic methods, to study HSC kinetics in vivo. The average replication rate for baboon HSCs is once per 36 weeks according to gene-marking analyses and once per 23 weeks according to telomere-shortening analyses. Comparable results were derived from the macaque data. These rates are substantially slower than the average replication rates previously reported for HSCs in mice (once per 2.5 weeks) and cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years, much longer than mice (∼2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number (∼80-200) of lifetime replications. Thus, our data suggest that the self-renewal capacity of mammalian stem cells in vivo is defined and evolutionarily conserved.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-02-075382