Tissue engineering of skeletal muscle. For patients with facial paralysis

PhD ceremony: Ms. M. Koning, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Tissue engineering of skeletal muscle. For patients with facial paralysis

Promotor(s): prof. P.M.N. Werker, prof. M.J.A. van Luyn

Faculty: Medical Sciences

Significant loss of functional muscle tissue has a profound impact on a patient’s life due to the limited capacity of self-repair of the muscle. In a world where millions are spent on appearance, an asymmetric, paralyzed face causes severe physical, social and psychological distress. The generation of skeletal muscle tissue using tissue engineering methods holds promise for future treatment of patients with facial paralysis. The main objective of this thesis was to improve tissue engineering of human skeletal muscle by providing new fundamental insights and tools. We show that human satellite cells are most suitable as a source for tissue engineering of autologous human skeletal muscle. In vitro cloned human satellite cells differentiate into either myotubes, which are immature muscle fibers, or new quiescent satellite cells. By manipulating the regulatory mechanism at post-transcriptional level through microRNAs, we can improve muscle fiber formation. Especially in elderly patient this therapeutic application is important since the regenerative capacity of our satellite cells declines during aging. Another important issue is that satellite cells, upon implantation, encounter an oxygen-deficient environment. We show that human satellite cells are resistant to an oxygen-deficient environment and in vivo differentiate into muscle fibers and quiescent satellite cells. Moreover, these muscle fibers are also well vascularized. In conclusion, our new insights and tools provide a solid basis for tissue engineering of human skeletal muscle from human satellite cells for patients with facial paralysis.