Delivery of therapeutic proteins from genetically engineered and implanted autologous cells offers the possibility of a more physiological mode of protein delivery than currently used repetitive needle injections. Proliferating human myogenic cells genetically engineered ex vivo to express recombinant human Factor VIII will be tissue engineered ex vivo into human 'bioartificial muscles' (HBAMs) containing organized postmitotic muscle fibers. Multiple BAMs will be attached under tension to resorbable vasculogenic scaffolds and implanted into an immunodeficient mouse model. Development of a functional interface between host blood vessels and the genetically engineered HBAMs will be assessed immunohistolochemically and by circulating plasma levels of rhFVIII. Reversibility of the therapy will be determined by removal of the implants after 30-60 days in vivo. Predictive in vivo dosage based on preimplant rhFVIII secretion levels will be determined by implantation of four to twelve HBAMs per animal. Successful completion of this project will allow the development of a reversible ex vivo gene therapy method to treat hemophilia A. ? ? ?
| Thorrez, Lieven; Shansky, Janet; Wang, Lin et al. (2008) Growth, differentiation, transplantation and survival of human skeletal myofibers on biodegradable scaffolds. Biomaterials 29:75-84 |
