SCID MOUSE MODELS OF HUMAN STEM-CELL ENGRAFTMENT

Citation
Dl. Greiner et al., SCID MOUSE MODELS OF HUMAN STEM-CELL ENGRAFTMENT, Stem cells, 16(3), 1998, pp. 166-177
Citations number
120
Categorie Soggetti
Oncology,"Cell Biology","Biothechnology & Applied Migrobiology","Developmental Biology
Journal title
ISSN journal
10665099
Volume
16
Issue
3
Year of publication
1998
Pages
166 - 177
Database
ISI
SICI code
1066-5099(1998)16:3<166:SMMOHS>2.0.ZU;2-9
Abstract
The discovery of the severe combined immunodeficiency (scid) mouse mut ation has provided a tool for establishment of small animal models as hosts for the in vivo analysis of normal and malignant human pluripote nt hemopoietic stem cells. Intravenous injection of irradiated scid mi ce with human bone marrow, cord blood, or G-CSF cytokine-mobilized per ipheral blood mononuclear cells, all rich in human hemopoietic stem ce ll activity, results in the engraftment of a human hemopoietic system in the murine recipient. This model has been used to identify a plurip otent stem cell, termed ''scid-repopulating cell'' (SRC) that is more primitive than any of the hemopoietic stem cell populations identified using the currently available in vitro methodology, In this review, w e describe the development and use of this model system, termed Hu-SRC -SCID, and summarize the discoveries that have resulted from the inves tigation of human stem cells in this model. Finally, we detail the rec ent extension of the original Hu-SRC-SCID model system based on the C. B-17-scid mouse as the murine host to the Hu-SRC-NOD-SCID model based on the NOD-scid mouse as the host. The engraftment of human stem cells in the Hu-SRC-NOD-SCID model is enhanced over that observed in the Hu -SRC-SCID model and results in exceptionally high levels of human hemo poietic cells in the murine recipient, Future directions to further im prove the Hu-SRC-NOD-SCID model system and the potential utility of th is model in the preclinical and diagnostic arenas of hematology and on cology are discussed.