Endothelial progenitor cell-based therapy for hemophilia A.

As shown by the results of both pre-clinical and clinical studies reported in past decades, the goal of establishing an effective and successful gene therapy for hemophilia A remains feasible and realistic. However, at this time, no single approach has been shown to be clearly superior, and a number of recurring challenges remain to be overcome. Given the persistent problems presented by the host immune response to systemic in vivo gene delivery, and the additional obstacles of inadequate transgene delivery and expression, we propose a re-evaluation of an ex vivo gene transfer approach that utilizes a genetically modified stem cell population. In this strategy, autologous blood outgrowth endothelial progenitor cells are obtained from hemophilic animals, into which a normal copy of the factor VIII gene is introduced via an engineered virus. Cell numbers are expanded in culture prior to their re-implantation under the skin of the hemophilic animals in an artificially developed supporting environment. Follow-up assessment of the treatment involves the general evaluation of clotting activity, the specific measurement of factor VIII levels in the blood, and clinical observation.