Providing a Microenvironment for the Development of Human CD34+ Hematopoietic Cells in SCID Mice.
In order to develop a convenient small-animal model that can support the differentiation of human bone-marrow-derived CD34+ cells, we transplanted SCID mice with an immortalized human stromal cell line, Lof(11-10). The Lof(11-10) cell line has been characterized to produce human cytokines capable of supporting primitive human hematopoietic cell proliferation in vitro. Intraperitoneal injection of Lof(11-10) cells into irradiated SCID mice by itself resulted in a dose-dependent survival of the mice from lethal irradiation. The radioprotective survival was reflected by an increase in the growth and number of mouse bone-marrow-derived committed hematopoietic progenitors. The Lof(11-10) cells localized to the spleen, but not to the bone marrow of these animals and resulted in detectable levels of circulating human IL-6 in their plasma. Secondary intravenous injections of either human or simian CD34+ cells into the Lof(11-10)-transplanted SCID mice resulted in engraftment of injected cells within the bone marrow of these mice. The utility of this small-animal model that allows the growth and differentiation of human CD34+ cells and its potential use in clinical gene therapy protocols are discussed. Copyright 1997 S. Karger AG, Basel
Kaushal
S.
S
Henry M. Jackson Foundation for the Advancement of Military Medicine and Walter Reed Army Institute of Research, Rockwille, Md., USA.
La Russa
V.F.
VF
Hall
E.R.
ER
Gartner
S.
S
Kim
J.H.
JH
Perera
L.P.
LP
Yu
Z.
Z
Kessler
S.W.
SW
Mosca
J.D.
JD