Submission
| Title: | Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis |
| Presenter: | Samuel Kaefer |
| Institution: | Indiana University School of Medicine |
| Authors: | Samuel L. Kaefer, BA ; Lujuan Zhang, MD ; Rachel A. Morrison, PhD ; Sarah Brookes, DVM, PhD Oluwaseyi Awonusi, MD; Elizabeth Shay, MD; Orlando S. Hoilett, PhD ; Jennifer L. Anderson, PhD Craig J. Goergen, PhD ; Sherry Voytik-Harbin, PhD; Stacey Halum, MD, FACS
From the School of Medicine (S.L.K., O.A., S.H.), Indiana University, Indianapolis, Indiana, U.S.A.; Weldon School of Biomedical Engineering (S.L.K., R.A.M., S.B., O.S.H., J.L.A., C.J.G., S.V.-H.), Purdue University, West Lafayette, Indiana, U.S.A.; School of Medicine, Department of Otolaryngology-Head and Neck Surgery (L.Z., E.S., S.H.), Indiana University, Indianapolis, Indiana, U.S.A.; Department of Biomedical Engineering (O.S.H.), University of Cincinnati, Cincinnati, Ohio, U.S.A.; Department of Basic Medical Sciences (S.V.-H.), Purdue University, West Lafayette, Indiana, U.S.A.; and the Department of Speech, Language, and Hearing Sciences (S.H.), Purdue University, West Lafayette, Indiana, U. S.A. |
Abstract
| Background/Significance/Rationale: | No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implica tions of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. |
| Methods: | Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. |
| Results/Findings: | MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of video- laryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. |
| Conclusions/Discussion: | Minimally invasive MEE injection appears to establish an early molecular and microenvironmental frame- work to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction. |
| Translational/Human Health Impact: | With the porcine larynx being comparable in size to that of humans, this study encapsulates an effective translational model for studying unilateral vocal fold paralysis. Herein, we demonstrate the molecular potential of MEEs and show a successful step in preclinical study of this biotherapeutic technique. |
