(471d) Engineering the Skeletal Muscle for Improved Innervation after Peripheral Nerve Injury
AIChE Annual Meeting
Wednesday, November 16, 2022 - 9:06am to 9:28am
To study the effect of NANOG on skeletal muscle innervation, we generated a mouse model (Col1a1-tetO-Nanog, in the ROSA26 locus, hereafter referred to as ROSA-NANOG) in which NANOG expression can be induced upon exposure to doxycycline (Dox). To limit NANOG expression only in the muscle, a slow-release polymer (Elvax), was implanted subcutaneously near the tibialis anterior (TA) muscle for 2 weeks. Elvax implantation was accompanied by sciatic nerve transection and end-to-end repair in both ROSA-NANOG and wild type (WT). WT served as controls. Needle electromyography (EMG) recordings demonstrated that ROSA-NANOG mice elicited almost 3x increase in EMG amplitude as compared to WT mice 16wks post nerve injury, confirming improved reinnervation is a result of re-engineering the muscle to a permissible state. This functional recovery in muscle activity on nerve stimulation accompanied significant improvements in the toe-spread reflex of ROSA-NANOG mice at both 5wks and 16wks post injury. Interestingly, we found that NANOG expression in the muscle prevented atrophy and resulted in increased isometric force production as compared to wild type animals. Further, we performed whole muscle immunohistochemistry to quantify the overlap of muscular acetylcholine receptors (AChRs) with neurofilament and synaptic vesicles. Indeed, while there was very limited presynaptic overlap in WT muscle, ROSA-NANOG mice demonstrated extensive overlap between synaptic vesicles and AChRs indicating restored innervation. In conclusion, we demonstrate that re-engineering the muscle by ectopic NANOG expression can improve functional outcomes after PNI.