Post-Chemotherapeutic Hematopoietic Reconstitution: A Transgenic Mouse Model

摘要

To improve the treatment of breast cancer, it is imperative to address specificshortcomings 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. We have developed both CD7 transgenic mouse and CD7 knockout mice as in vivo models for studying hematopoietic progenitor cell differentiation and the cytokines which regulate proliferation and differentiation of these progenitors. Work has also been initiated for development of mouse CD7 antibodies. These antibodies will allow selection of mouse multipotent hematopoietic progenitor cell populations that express the CD7 gene and which in humans are not stem cells, yet are multipotent. 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 identified numerous conserved functional sequence elements. These models should provide clinically relevant information about control of hematopoiesis.