|
|
 Previous Article | Table of Contents | Next Article 
Human allogeneic stem cell maintenance and differentiation in a long- term
multilineage SCID-hu graft
CC Fraser, H Kaneshima, G Hansteen, M Kilpatrick, R Hoffman and BP Chen
Experimental Cell Therapy Group, SyStemix Inc, Palo Alto, CA 94304, USA.
The ability to determine the functional capacity of putative human
hematopoietic stem cell (HSC) populations requires in vivo assays in which
long-term multilineage differentiation can be assessed. We hypothesized
that if human fetal bone was transplanted adjacent to a fetal thymus
fragment in severe combined immunodeficient (SCID) mice, a conjoint organ
might form in which HSC in the human bone marrow (BM) would mimic human
multilineage differentiation into progenitor cells, B cells, and myeloid
cells; undergo self-renewal; and migrate to and differentiate into T cells
within the thymic microenvironment. To test this possibility, SCID mice
were transplanted subcutaneously with HLA class I mismatched fetal bone,
thymus, and spleen fragments (SCID-hu BTS). We found that the BM of SCID-hu
BTS grafts maintained B cells, myeloid cells, CD34+ cells for at least 36
weeks posttransplant. Assayable hematopoietic progenitors colony-forming
units-granulocyte- macrophage were present in 100% (66/66) of grafts over a
period of 28 weeks. Cells with a HSC phenotype (CD34+Thy-1+Lin-) were
maintained for 20 weeks in SCID-hu BTS grafts. These CD34+Thy-1+Lin- cells
had potent secondary multilineage reconstituting potential when isolated
and injected into a secondary HLA mismatched SCID-hu bone assay and
analyzed 8 weeks later. In addition, early progenitors within the BM of
SCID-hu BTS grafts were capable of migrating to the human thymus and
undergoing differentiation through immature CD4+CD8+ double-positive T
cells and produce mature T cells with a CD4+CD8- or CD8+CD4- phenotype that
could be detected for at least 36 weeks. Phenotypically defined human fetal
liver (FL) and umbilical cord blood (UCB) hematopoietic stem cell
populations were injected into irradiated SCID-hu BTS grafts to assess
their multilineage repopulating capacity and to assess the ability of the
BTS system to provide an environment where multiple lineages might
differentiate from a common stem cell pool. Injection of irradiated grafts
with FL HSC or UCB HSC cells resulted in donor- derived B cells, myeloid
cells, immature and mature T cells, and CD34+ cells in individual grafts
when analyzed 8 weeks postreconstitution, further showing the
multipotential nature of these stem cell populations. In addition, a strong
correlation was observed between maintenance of host graft-derived CD8+
cells and failure of donor stem cell engraftment.(ABSTRACT TRUNCATED AT 400
WORDS)
Volume 86,
Issue 5,
pp. 1680-1693,
09/01/1995
Copyright © 1995 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. Feuring-Buske and D. E. Hogge
Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34+CD38{-} progenitor cells from patients with acute myeloid leukemia
Blood,
June 15, 2001;
97(12):
3882 - 3889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nagano, J. R. McCarrey, and R. L. Brinster
Primate Spermatogonial Stem Cells Colonize Mouse Testes
Biol Reprod,
May 1, 2001;
64(5):
1409 - 1416.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. S. Rosler, J. E. Brandt, J. Chute, and R. Hoffman
An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells
Blood,
November 15, 2000;
96(10):
3414 - 3421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Punzel, S.D. Wissink, J.S. Miller, K.A. Moore, I.R. Lemischka, and C.M. Verfaillie
The Myeloid-Lymphoid Initiating Cell (ML-IC) Assay Assesses the Fate of Multipotent Human Progenitors In Vitro
Blood,
June 1, 1999;
93(11):
3750 - 3756.
[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]
|
|
|
|
|
|
|
M. M.A. Verstegen, P. B. van Hennik, W. Terpstra, C. van den Bos, J. J. Wielenga, N. van Rooijen, R. E. Ploemacher, G. Wagemaker, and A. W. Wognum
Transplantation of Human Umbilical Cord Blood Cells in Macrophage-Depleted SCID Mice: Evidence for Accessory Cell Involvement in Expansion of Immature CD34+CD38- Cells
Blood,
March 15, 1998;
91(6):
1966 - 1976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Rappold, B. L. Ziegler, I. Kohler, S. Marchetto, O. Rosnet, D. Birnbaum, P. J. Simmons, A. C.W. Zannettino, B. Hill, S. Neu, et al.
Functional and Phenotypic Characterization of Cord Blood and Bone Marrow Subsets Expressing FLT3 (CD135) Receptor Tyrosine Kinase
Blood,
July 1, 1997;
90(1):
111 - 125.
[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]
|
|
|
|
|
|
|
S. Yurasov, T. R. Kollmann, A. Kim, C. A. Raker, M. Hachamovitch, F. Wong-Staal, and H. Goldstein
Severe Combined Immunodeficiency Mice Engrafted With Human T Cells, B Cells, and Myeloid Cells After Transplantation With Human Fetal Bone Marrow or Liver Cells and Implanted With Human Fetal Thymus: A Model for Studying Human Gene Therapy
Blood,
March 1, 1997;
89(5):
1800 - 1810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
