|
|
Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-07-2024.
 Previous Article | Table of Contents | Next Article 
Blood, 1 July 2003, Vol. 102, No. 1, pp. 127-135
HEMATOPOIESIS
Human NK cell development in NOD/SCID mice receiving grafts of cord blood CD34+ cells
Christian P. Kalberer,
Uwe Siegler, and
Aleksandra Wodnar-Filipowicz
From the Laboratory of Experimental Hematology, Department of Research, University Hospital Basel, Switzerland.
Definition of the cytokine environment, which regulates the maturation of human natural killer (NK) cells, has been largely based on in vitro assays because of the lack of suitable animal models. Here we describe conditions leading to the development of human NK cells in NOD/SCID mice receiving grafts of hematopoietic CD34+ precursor cells from cord blood. After 1-week-long in vivo treatment with various combinations of interleukin (IL)–15, flt3 ligand, stem cell factor, IL-2, IL-12, and megakaryocyte growth and differentiation factor, CD56+CD3- cells were detected in bone marrow (BM), spleen, and peripheral blood (PB), comprising 5% to 15% of human CD45+ cells. Human NK cells of NOD/SCID mouse origin closely resembled NK cells from human PB with respect to phenotypic characteristics, interferon (IFN)– production, and cytotoxicity against HLA class 1–deficient K562 targets in vitro and antitumor activity against K562 erythroleukemia in vivo. In the absence of growth factor treatment, CD56+ cells were present only at background levels, but CD34+CD7+ and CD34-CD7+ lymphoid precursors with NK cell differentiation potential were detected in BM and spleen of chimeric NOD/SCID mice for up to 5 months after transplantation. Our results demonstrate that limitations in human NK cell development in the murine microenvironment can be overcome by treatment with NK cell growth–promoting human cytokines, resulting in the maturation of IFN-–producing cytotoxic NK cells. These studies establish conditions to explore human NK cell development and function in vivo in the NOD/SCID mouse model. (Blood. 2003;102:127-135)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. S. Woll, B. Grzywacz, X. Tian, R. K. Marcus, D. A. Knorr, M. R. Verneris, and D. S. Kaufman
Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity
Blood,
June 11, 2009;
113(24):
6094 - 6101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bridenbaugh, L. Kenins, E. Bouliong-Pillai, C. P. Kalberer, E. Shklovskaya, A. Gratwohl, and A. Wodnar-Filipowicz
Clinical stem-cell sources contain CD8+CD3+ T-cell receptor-negative cells that facilitate bone marrow repopulation with hematopoietic stem cells
Blood,
February 1, 2008;
111(3):
1735 - 1738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Sun, H. Wei, R. Sun, W. Xiao, Y. Yang, and Z. Tian
Human Interleukin-15 Improves Engraftment of Human T Cells in NOD-SCID Mice
Clin. Vaccine Immunol.,
February 1, 2006;
13(2):
227 - 234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Nowbakht, M.-C. S. Ionescu, A. Rohner, C. P. Kalberer, E. Rossy, L. Mori, D. Cosman, G. De Libero, and A. Wodnar-Filipowicz
Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias
Blood,
May 1, 2005;
105(9):
3615 - 3622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Chklovskaia, P. Nowbakht, C. Nissen, A. Gratwohl, M. Bargetzi, and A. Wodnar-Filipowicz
Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand
Blood,
May 15, 2004;
103(10):
3860 - 3868.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
