Post-Chemotherapeutic Hematopoietic Reconstitution: A Transgenic Mouse Model.
Annual rept. 1 Aug 94-31 Jul 95,
DUKE UNIV DURHAM NC
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To improve the treatment of breast cancer, it is imperative to address specific shortcomings in autologous bone marrow reconstitution, in particular the frequent failure to reconstitute specific hematopoietic lineages and the length of time required to restore immunocompetence after transplant. Previous studies have shown that the CD7 protein in human identifies multipotent progenitor cells of T-, B- and myeloid. We have developed a novel CD7 transgenic mouse as an in vivo model for studying both hematopoietic progenitor cell differentiation and the cytokines which regulate proliferation and progenitor cell differentiation of these progenitors. This mouse model is unique in that it allows selection of mouse multipotent hematopoietic progenitor cell populations that express the CD7 gene and which are not stem cells, yet multipotent in humans. Characterization of these cell populations and their growth and differentiation factors will allow both the transplant of more mature progenitor populations to speed engraftment. In addition, we have cloned and sequenced the recently described mouse CD7 gene, and have identifies numerous conserved functional sequence elements. These models should provide clinically relevant information about control of hematopoiesis, difficult to obtain directly in humans, and it may allow development of novel methods for current breast cancer treatment protocols.
- Anatomy and Physiology