|
|
 Previous Article | Table of Contents | Next Article 
Engraftment of human hematopoietic precursor cells with secondary transfer
potential in SCID-hu mice
BP Chen, A Galy, S Kyoizumi, R Namikawa, J Scarborough, S Webb, B Ford, DZ Cen and SC Chen
SyStemix Inc, Palo Alto, CA 94304.
Human fetal bone fragments implanted subcutaneously in immunodeficient
(SCID) mice maintain active human hematopoiesis. In this study, we show
that this human hematopoietic microenvironment supports the engraftment and
differentiation of HLA-mismatched, CD34+ primitive hematopoietic progenitor
cells isolated from fetal and adult human bone marrow (BM). The BM CD34+
cells were depleted of CD2, CD14, CD15, CD16, glycophorin A, and CD19
lineage-committed cells (CD34+Lin-). Donor cell engraftment was manifested
by the presence of B (CD19+) and myeloid (CD33+) cells of donor HLA
phenotype. Successful engraftment was observed as early as 4 weeks after
fetal BM donor cell injection and sustained for at least 12 weeks, with
engraftment success rates of 100% (11/11 grafts) and 92% (11/12 grafts) at
8 and 12 weeks, respectively. Mixed BM chimerism of donor and endogenous
cells was consistently observed in SCID-hu bones successfully engrafted
with HLA-mismatched CD34+Lin- donor cells. Preconditioning of the SCID-hu
bone with a single dose of sublethal (350 rad) whole body irradiation (WBI)
immediately before cell injection enhanced the repopulation of the bone
grafts with donor cells and, in some instances, resulted in complete
repopulation. After WBI, as few as 500 fetal bone marrow CD34+Lin- cells
injected in the human bone grafts resulted in donor-derived hematopoiesis.
Donor progenitor cells recovered from the SCID-hu bone grafts 8 weeks
postinjection had the capacity to repopulate secondary groups of
HLA-disparate fetal human bones in SCID-hu mice with B and myeloid cells as
well as CD34+ cells in some recipients. In addition, these cells
repopulated fetal human thymus fragments in SCID mice with donor thymocytes
including immature CD4+CD8+ and mature CD4+CD8- as well as CD4-CD8+
subsets. These results indicate that the fetal human bone implants of
SCID-hu mice can support the maintenance of a cell population that has both
multilineage potential and repopulating potential for periods of time as
long as 16 weeks. The SCID-hu bone model consistently supported the
engraftment of both fetal and adult CD34+Lin- cells without the
administration of exogenous human cytokines to these animals. This model is
currently being used to permit the isolation and characterization of
candidate human hematopoietic stem cells (HSCs) and provide important
information critical for human HSC therapy in humans.
Volume 84,
Issue 8,
pp. 2497-2505,
10/15/1994
Copyright © 1994 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. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, P. Lin, Y. Shi, J. Romaguera, L. W. Kwak, et al.
A Severe Combined Immunodeficient-hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma
Clin. Cancer Res.,
April 1, 2008;
14(7):
2154 - 2160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, P. Neri, J. L. Kutok, O. Tournilhac, D. D. Santos, E. Hatjiharissi, V. Munshi, S. Venuta, K. C. Anderson, S. P. Treon, et al.
A SCID-hu in vivo model of human Waldenstrom macroglobulinemia
Blood,
August 15, 2005;
106(4):
1341 - 1345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, P. Neri, D. R. Carrasco, R. Burger, V. S. Goldmacher, R. Fram, V. Munshi, M. A. Shammas, L. Catley, G. S. Jacob, et al.
A clinically relevant SCID-hu in vivo model of human multiple myeloma
Blood,
July 15, 2005;
106(2):
713 - 716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, V. S. Goldmacher, P. Neri, A. Gozzini, M. A. Shammas, K. R. Whiteman, L. L. Hylander-Gans, D. R. Carrasco, T. Hideshima, R. Shringarpure, et al.
Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells
Blood,
December 1, 2004;
104(12):
3688 - 3696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Shih, Y. Weng, A. Mamelak, T. LeBon, M. C.-T. Hu, and S. J. Forman
Identification of a candidate human neurohematopoietic stem-cell population
Blood,
October 15, 2001;
98(8):
2412 - 2422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Shih, M. C.-T. Hu, J. Hu, Y. Weng, P. J. Yazaki, J. Medeiros, and S. J. Forman
A secreted and LIF-mediated stromal cell-derived activity that promotes ex vivo expansion of human hematopoietic stem cells
Blood,
March 15, 2000;
95(6):
1957 - 1966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-C. Shih, M. C.-T. Hu, J. Hu, J. Medeiros, and S. J. Forman
Long-Term Ex Vivo Maintenance and Expansion of Transplantable Human Hematopoietic Stem Cells
Blood,
September 1, 1999;
94(5):
1623 - 1636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Greiner, R. A. Hesselton, and L. D. Shultz
SCID Mouse Models of Human Stem Cell Engraftment
Stem Cells,
May 1, 1998;
16(3):
166 - 177.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. M. Luens, M. A. Travis, B. P. Chen, B. L. Hill, R. Scollay, and L. J. Murray
Thrombopoietin, kit Ligand, and flk2/flt3 Ligand Together Induce Increased Numbers of Primitive Hematopoietic Progenitors From Human CD34+Thy-1+Lin- Cells With Preserved Ability to Engraft SCID-hu Bone
Blood,
February 15, 1998;
91(4):
1206 - 1215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Urashima, B. P. Chen, S. Chen, G. S. Pinkus, R. T. Bronson, D. A. Dedera, Y. Hoshi, G. Teoh, A. Ogata, S. P. Treon, et al.
The Development of a Model for the Homing of Multiple Myeloma Cells to Human Bone Marrow
Blood,
July 15, 1997;
90(2):
754 - 765.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Berardi, E. Meffre, F. Pflumio, A. Katz, W. Vainchenker, C. Schiff, and L. Coulombel
Individual CD34+CD38lowCD19-CD10- Progenitor Cells From Human Cord Blood Generate B Lymphocytes and Granulocytes
Blood,
May 15, 1997;
89(10):
3554 - 3564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Havenga, P. Hoogerbrugge, D. Valerio, and H. H.G. van Es
Retroviral Stem Cell Gene Therapy
Stem Cells,
May 1, 1997;
15(3):
162 - 179.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. Su, R. Lee, M. Bonyhadi, H. Matsuzaki, S. Forestell, S. Escaich, E. Bohnlein, and H. Kaneshima
Hematopoietic Stem Cell-Based Gene Therapy for Acquired Immunodeficiency Syndrome: Efficient Transduction and Expression of RevM10 in Myeloid Cells In Vivo and In Vitro
Blood,
April 1, 1997;
89(7):
2283 - 2290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O. Muench, M. G. Roncarolo, and R. Namikawa
Phenotypic and Functional Evidence for the Expression of CD4 by Hematopoietic Stem Cells Isolated From Human Fetal Liver
Blood,
February 15, 1997;
89(4):
1364 - 1375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Namikawa, M. Muench, and M. Roncarolo
Regulatory roles of the ligand for Flk2/Flt3 tyrosine kinase receptor on human hematopoiesis
Stem Cells,
July 1, 1996;
14(4):
388 - 395.
[Abstract]
|
|
|
|
|
