|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2829-2837
Effects of cell cycle activation on the short-term engraftment
properties of ex vivo expanded murine hematopoietic cells
Stephen J. Szilvassy,
Todd E. Meyerrose, and
Barry Grimes
From the Blood and Marrow Transplant Program, the Division of
Hematology/Oncology, Lucille P. Markey Cancer Center,
University of Kentucky, Lexington, KY.
Loss of long-term hematopoietic stem cell function in vitro is
associated with cell cycle progression. To determine whether cytokine-induced proliferation also limits the rate of short-term engraftment and potential clinical utility of ex vivo expanded hematopoietic cells, murine
Sca-1+c-kit+Lin cells were
cultured in interleukin-6 (IL-6), IL-11, granulocyte colony-stimulating
factor (G-CSF), stem cell factor, flk-2 ligand, and
thrombopoietin for 7 days. Cells amplified 2000-fold were then stained
with Hoechst 33342, separated into G0/G1 (72% ± 3%) or S/G2/M (27% ± 3%) fractions by flow
sorting, and injected into lethally irradiated mice. Although long-term
(more than 6 months) engraftment of lymphoid and myeloid lineages was
greater in primary and secondary recipients of expanded cells residing
in G0/G1 at the time of transplantation, there
were no noted differences in the short-term (less than 6 weeks)
recovery kinetics of circulating blood cells. When hematopoietic cells
were expanded in cultures containing the tetrapeptide stem cell
inhibitor N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) to reduce progenitor
cycling prior to transplantation, again there were no differences
observed in short-term reconstitution by inhibited or uninhibited
cells. Interestingly, AcSDKP significantly accelerated engraftment by
expanded hematopoietic cells when administered in vivo at the time of
transplantation. Leukocytes recovered to 20% of normal levels
approximately 1 week faster, and thrombocytopenia was largely abrogated
in AcSDKP-treated versus untreated mice. Therefore, while AcSDKP can
accelerate the engraftment of ex vivo expanded hematopoietic
progenitors, which suggests a relatively simple approach to improve
their clinical utility, its effects appear unrelated to cell cycle arrest.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. Rezzoug, Y. Huang, M. K. Tanner, M. Wysoczynski, C. L. Schanie, P. M. Chilton, M. Z. Ratajczak, I. J. Fugier-Vivier, and S. T. Ildstad
TNF-{alpha} Is Critical to Facilitate Hemopoietic Stem Cell Engraftment and Function
J. Immunol.,
January 1, 2008;
180(1):
49 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Dao and J. A. Nolta
Cytokine and integrin stimulation synergize to promote higher levels of GATA-2, c-myb, and CD34 protein in primary human hematopoietic progenitors from bone marrow
Blood,
March 15, 2007;
109(6):
2373 - 2379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Nygren, D. Bryder, and S. E. W. Jacobsen
Prolonged Cell Cycle Transit Is a Defining and Developmentally Conserved Hemopoietic Stem Cell Property
J. Immunol.,
July 1, 2006;
177(1):
201 - 208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Lee, S. C. Hsu, J. Munoz, J. S. Jung, N. R. Lee, R. Pochampally, and D. J. Prockop
A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice
Blood,
March 1, 2006;
107(5):
2153 - 2161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. F. Srour, X. Tong, K. W. Sung, P. A. Plett, S. Rice, J. Daggy, C. T. Yiannoutsos, R. Abonour, and C. M. Orschell
Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38-/lo cells in G0
Blood,
April 15, 2005;
105(8):
3109 - 3116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ahmed, S. J. Ings, A. R. Pizzey, M. P. Blundell, A. J. Thrasher, H. T. Ye, A. Fahey, D. C. Linch, and K. L. Yong
Impaired bone marrow homing of cytokine-activated CD34+ cells in the NOD/SCID model
Blood,
March 15, 2004;
103(6):
2079 - 2087.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. D. Helgason, J. Antonchuk, C. Bodner, and R. K. Humphries
Homeostasis and regeneration of the hematopoietic stem cell pool are altered in SHIP-deficient mice
Blood,
November 15, 2003;
102(10):
3541 - 3547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Liu, F. Lawrence, M. Kovacevic, J. Bignon, E. Papadimitriou, J.-Y. Lallemand, P. Katsoris, P. Potier, Y. Fromes, and J. Wdzieczak-Bakala
The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo
Blood,
April 15, 2003;
101(8):
3014 - 3020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Quesenberry, G. A. Colvin, and J.-F. Lambert
The chiaroscuro stem cell: a unified stem cell theory
Blood,
December 15, 2002;
100(13):
4266 - 4271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wilpshaar, M. Bhatia, H. H. H. Kanhai, R. Breese, D. K. Heilman, C. S. Johnson, J. H. F. Falkenburg, and E. F. Srour
Engraftment potential of human fetal hematopoietic cells in NOD/SCID mice is not restricted to mitotically quiescent cells
Blood,
June 17, 2002;
100(1):
120 - 127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Giet, D. R. Van Bockstaele, I. Di Stefano, S. Huygen, R. Greimers, Y. Beguin, and A. Gothot
Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells
Blood,
March 15, 2002;
99(6):
2023 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Szilvassy, T. E. Meyerrose, P. L. Ragland, and B. Grimes
Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver
Blood,
October 1, 2001;
98(7):
2108 - 2115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
