Tissue engineering of human muscle: proof of principle for using iPSC-derived myogenic precursor cells and a prevascularization strategy.

We will expand further on an existing 3D human muscle tissue engineering method. Current state of the art is that such muscle can be made up of aligned myofibers in an extracellular matrix. The size of these muscles that can be reached without inducing cell death in the inner part is limited due to the passive diffusion limit of oxygen and nutrients to the myofibers. By addition of endothelial precursor cells, we have shown it is possible to create endothelial networks interspersed with muscle fibers. Although cocultures of myoblasts and endothelial cells were sustained in vitro, functionality of these networks has not been shown thus far in vivo.

Currently, human muscle are engineered from primary satellite cells. However, use of myogenic precursor cells differentiated from human induced pluripotent stem cells (iPSC) provides a highly attractive alternative. Indeed, this would enable creating patient-specific muscle tissue.

The current proposal aims at delivering proof-of-principle that human muscle can be created in vitro from induced pluripotent stem cells and can be engineered to include endothelial networks which are functional in vivo.