Abstract
Abstract SCI-42
“Self-renewal” is a process central to the expansion of normal and cancerous stem cells and its understanding is critical for future advances in transplantation-based therapies and cancer treatment. Even today, many patients are deprived of the benefit of a successful blood stem cell transplant because the number of allogeneic or autologous stem cells available is insufficient, which results in delayed hematopoietic recovery post-transplant, or exclusion of a transplant-based therapeutic option altogether. The molecular machinery controlling self-renewal of hematopoietic stem cells (HSCs) remains poorly defined with the exception of a few genes such as HOX4 and Bmi1. We and others recently demonstrated the capacity of a recombinant HOXB4 protein (TAT-HOXB4 fusion protein) to stimulate mouse and human HSC self-renewal divisions in culture. Technical difficulties inherent to this recombinant protein have postponed the initiation of clinical trials. In part to overcome this hurdle, we have developed a novel in vitro/in vivo gain-of-function screen and identified several nuclear factors which expand hematopoietic stem cell ex vivo. A significant proportion of these factors display HOXB4-like properties and show non-cell autonomous activity. Initial results suggest that some of these new factors are also active with human cord blood derived HSCs. The generation of novel TAT fusion proteins will open new possibilities in the therapeutic expansion of human HSCs.
No relevant conflicts of interest to declare.
