Angiogenesis Enhances Factor IX Delivery and Persistence from Retrievable Human Bioengineered Muscle Implants

Lieven Thorrez, Herman Vandenburgh, Nico Callewaert, Nico Mertens, Janet Shansky, Lin Wang, Jef Arnout, Désiré Collen, Marinee Chuah, Thierry VandenDriessche
2006 Molecular Therapy  
Human muscle progenitor cells transduced with lentiviral vectors secreted high levels of blood clotting factor IX (FIX). When bioengineered into postmitotic myofibers as human bioartificial muscles (HBAMs) and subcutaneously implanted into immunodeficient mice, they secreted FIX into the circulation for N3 months. The HBAM-derived FIX was biologically active, consistent with the cells' ability to conduct the necessary posttranslational modifications. These bioengineered muscle implants are
more » ... evable, an inherent safety feature that distinguishes this "reversible" gene therapy approach from most other gene therapy strategies. When myofibers were bioengineered from human myoblasts expressing FIX and vascular endothelial growth factor, circulating FIX levels were increased and maintained long term within the therapeutic range, consistent with the generation of a vascular network around the HBAM. The present study implicates an important role for angiogenesis in the efficient delivery of therapeutic proteins using tissue engineered stem cellbased gene therapies.
doi:10.1016/j.ymthe.2006.03.019 pmid:16750937 fatcat:h544uexhzbhfpe27t27utew45m