Genetic marking as an approach to studying in vivo hematopoiesis: progress in the non-human primate model. Oncogene 2002 May 13;21(21):3274-83
Date
05/29/2002Pubmed ID
12032769DOI
10.1038/sj.onc.1205320Scopus ID
2-s2.0-0037071417 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Retroviral insertion site analysis following transplantation of marked hematopoietic stem cells (HSCs) is a powerful method for studying hematopoiesis in vivo. High-level gene transfer efficiency was achieved in murine models in the late 1980s, but early human gene transfer protocols into hematopoietic stem and progenitor cells using the murine methodology showed consistently poor results. The utility of non-human primates as pre-clinical models has since become apparent. Modifications in retroviral transduction conditions have resulted in stable long-term gene transfer efficiency as high as 15-20% to primitive repopulating cells in non-human primate models. This has permitted, for the first time in a large animal model, tracking of individual stem and progenitor cell clones via insertion site analysis, an advantage over competitive transplantation studies, which cannot firmly evaluate the number or life span of individual clones contributing to hematopoiesis. Retroviral tracking studies in mice suggest that stable hematopoiesis may be dominated by a small number of clones, but these studies have been limited by insensitive detection methods, low numbers of transplanted stem cells, and limited life span of immunodeficient mice. Autologous transplantation studies in non-human primates have just begun and have the potential to shed light on controversial issues such as the number of clones contributing to stable hematopoiesis, clonal succession, and lineage commitment, as well as the effect of clinically relevant manipulations such as cytokines, chemotherapy, and radiation on hematopoiesis. These approaches will have significant impact in studying various aspects of stem cell biology including the phenomenon of stem cell plasticity.
Author List
Shi PA, Hematti P, von Kalle C, Dunbar CEAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Lineage
Gene Transfer Techniques
Hematopoiesis
Hematopoietic Stem Cells
Humans
Models, Genetic
Primates