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Modeling human lymphoid precursor cell gene therapy in the SCID-hu mouse
RK Akkina, JD Rosenblatt, AG Campbell, IS Chen and JA Zack
Department of Medicine, UCLA School of Medicine 90024-1678.
Gene therapy of human T-lymphocyte disorders, including acquired
immunodeficiency syndrome (AIDS), would be greatly facilitated by the
development of an in vivo system in which transduced human hematopoietic
stem cells can be used to reconstitute the T-lymphoid compartment. Here we
use the SCID-hu mouse as a recipient for human CD34+ hematopoietic
progenitor cells transduced in vitro with a retroviral vector carrying the
neomycin resistance gene (neoR). The transduced cells engraft and
reconstitute the lymphoid compartments of the human thymus implant with as
few as 5 x 10(4) CD34+ cells. The neoR gene was expressed at low levels in
human thymocytes and there was no apparent effect on thymocyte
differentiation as a result of vector transduction. Thus, this SCID-hu
mouse system is the first in vivo model showing human thymopoiesis after
transduction of exogenous vectors, and should allow preclinical testing of
gene therapeutic reagents designed to function in human cells of the
T-lymphoid lineage. Because human immunodeficiency virus type 1 infection
induces depletion of human thymocytes in SCID-hu mice, this system may be
particularly valuable in evaluating efficacy of gene therapies to combat
AIDS.
Volume 84,
Issue 5,
pp. 1393-1398,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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