|
|
 Previous Article | Table of Contents | Next Article 
Phenotypic and functional characterization of long-term culture- initiating
cells present in peripheral blood progenitor collections of normal donors
treated with granulocyte colony-stimulating factor
F Prosper, D Stroncek and CM Verfaillie
Department of Medicine, University of Minnesota, Minneapolis, USA.
Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood
progenitor cells (PBPC) have successfully been used as stem cells for both
autologous and allogeneic transplants. However, little is known concerning
the absolute number and phenotype of primitive progenitors, such as
long-term culture-initiating cells (LTC-IC) in mobilized PBPC. The aim of
our study was to evaluate the capacity of G- CSF to mobilize LTC-IC in the
PB of normal individuals and to evaluate the phenotypic and functional
characteristics of G-CSF mobilized LTC- IC. G-CSF was administered to 29
healthy volunteers at 7.5 micrograms or 10 micrograms/kg/d subcutaneously
(SC) for 5 consecutive days and PBPC were harvested on day 6. Mobilization
with G-CSF increased the absolute number of week 5 LTC-IC in PB 60-fold,
while the number of CD34+ cells and committed colony forming cells (CFC)
was increased sevenfold to 12-fold. The frequency of CFC and week 5 LTC-IC
in CD34+ cells selected by fluorescence-activated cell sorter (FACS) from
mobilized PBPC was 2 +/- 0.3-fold and 9 +/- 2.2-fold higher respectively
than in CD34+ cells selected from unmobilized PBMNC. CFC were enriched in
the CD34+ CD38+ and CD34+ HLA-DR+ populations. The absolute number of
LTC-IC present in CD34+ CD38- and CD34+ HLA-DR- cells selected by FACS from
either mobilized PBPC, unmobilized PBMNC or steady state bone marrow (BM)
was similar (0.5% to 2%). In contrast to unmobilized PBMNC or steady state
BM CD34+ CD38+ and CD34+ HLA-DR+ cells, which contain less than 0.1%
LTC-IC, CD34+ CD38+ and CD34+ HLA- DR+ cells sorted from mobilized PBPC
contained 0.5% to 5% of cells capable of sustaining hematopoiesis in
long-term cultures for 5 weeks. However, 90% to 95% of LTC-IC present in
mobilized CD34+ CD38+ and CD34+ HLA-DR+ cells were not able to sustain
hematopoiesis for 8 weeks, while 30% of CD34+ CD38- and CD34+ HLA-DR-
LTC-IC present in mobilized PBPC could sustain hematopoiesis for at least 8
weeks. This suggests that the majority of CD34+ CD38+ and CD34+ HLA-DR+
week 5 LTC-IC represent progenitors at an intermediate state of
differentiation. We conclude that G-CSF effectively mobilizes LTC-IC in the
blood of normal individuals. Although a fraction of these cells has
functional characteristics similar to those of steady state PBMNC or BM
LTC-IC, more than 85% of mobilized PBPC LTC-IC are CD34+ CD38+ and CD34+
HLA- DR+, capable of sustaining hematopoiesis for 5 weeks, but not for 8
weeks. The functional and phenotypic characterization of primitive and more
mature populations of LTC-IC in mobilized PBPC should prove extremely
useful in future studies examining the role of these progenitors in
engraftment following transplantation.
Volume 88,
Issue 6,
pp. 2033-2042,
09/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Xu, E. Bruno, J. Chao, S. Huang, G. Finazzi, S. M. Fruchtman, U. Popat, J. T. Prchal, G. Barosi, R. Hoffman, et al.
Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases
Blood,
June 1, 2005;
105(11):
4508 - 4515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Tajima, T. Deguchi, J. H. Laver, H. Zeng, and M. Ogawa
Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells
Blood,
May 1, 2001;
97(9):
2618 - 2624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Glimm, I.-H. Oh, and C. J. Eaves
Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0
Blood,
December 15, 2000;
96(13):
4185 - 4193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Jiang, R. C. H. Zhao, and C. M. Verfaillie
Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity
PNAS,
September 5, 2000;
(2000)
190104497.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. F. Srour;, C. Eaves, and H. Glimm
Proliferative history and hematopoietic function of ex vivo expanded human CD34+ cells
Blood,
August 15, 2000;
96(4):
1609 - 1612.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Conneally, C.J. Eaves, and R.K. Humphries
Efficient Retroviral-Mediated Gene Transfer to Human Cord Blood Stem Cells With In Vivo Repopulating Potential
Blood,
May 1, 1998;
91(9):
3487 - 3493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Dooley, M. Xiao, B. K. Oppenlander, J. M. Plunkett, and S. D. Lyman
Flt3 Ligand Enhances the Yield of Primitive Cells After Ex Vivo Cultivation of CD34+ CD38dim Cells and CD34+ CD38dim CD33dim HLA-DR+ Cells
Blood,
November 15, 1997;
90(10):
3903 - 3913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, F. Prosper, and V. McCullar
Natural Killer (NK) Cells Are Functionally Abnormal and NK Cell Progenitors Are Diminished in Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Progenitor Cell Collections
Blood,
October 15, 1997;
90(8):
3098 - 3105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Conneally, J. Cashman, A. Petzer, and C. Eaves
Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice
PNAS,
September 2, 1997;
94(18):
9836 - 9841.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.L. Petzer, C.J. Eaves, M.J. Barnett, and A.C. Eaves
Selective Expansion of Primitive Normal Hematopoietic Cells in Cytokine-Supplemented Cultures of Purified Cells From Patients With Chronic Myeloid Leukemia
Blood,
July 1, 1997;
90(1):
64 - 69.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Prosper, K. Vanoverbeke, D. Stroncek, and C. M. Verfaillie
Primitive Long-Term Culture Initiating Cells (LTC-ICs) in Granulocyte Colony-Stimulating Factor Mobilized Peripheral Blood Progenitor Cells Have Similar Potential for Ex Vivo Expansion as Primitive LTC-ICs in Steady State Bone Marrow
Blood,
June 1, 1997;
89(11):
3991 - 3997.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Jiang, R. C. H. Zhao, and C. M. Verfaillie
Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity
PNAS,
September 12, 2000;
97(19):
10538 - 10543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
