Providing a microenvironment for the development of human CD34+ hematopoietic cells in SCID mice |
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| Authors: | Kaushal S La Russa V F Hall E R Gartner S Kim J H Perera L P Yu Z Kessler S W Mosca J D |
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| Institution: | (1) Henry M. Jackson Foundation for the Advancement of Military Medicine and Walter, Reed Army Institute of Research, Rockville, Md.;(2) Bone Marrow Transplantation Program, Tulane Cancer Center, New Orleans, La.;(3) The Johns Hopkins Hospital, Department of Neurology, University of Maryland at Baltimore, USA;(4) Institute for Human Virology, University of Maryland at Baltimore, USA;(5) National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Md.;(6) Systemix, Palo Alto, Calif., USA;(7) US Naval Medical Research Unit 3, Cairo, Egypt;(8) Osiris Therapeutics Inc., 2001 Aliceanna Street, 21231-2001 Baltimore, MD, USA |
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| Abstract: | 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. |
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| Keywords: | SCID mice Hematopoiesis Stromal cells CD34+ cells Microenvironment |
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