Application of SIS-ECM Constructs Laden with Gingiva-derived MSCs in Tongue Myomucosal Regeneration
Rabie M. Shanti is currently an Assistant Professor in Oral & Maxillofacial Surgery and Otorhinolaryngology/Head and Neck Surgery of University of Pennsylvania. He received his DMD degree from Harvard School of Dental Medicine and later received his MD degree from New Jersey Medical School-Newark in 2011. Dr. Shanti’s current clinical practices mainly focus on the reconstruction of patients with post-ablative or post-traumatic defects of the oral and maxillofacial region. His current research activities involve stem cell biology and regenerative medicine to improve the understanding of the pathogenesis of ameloblastoma in order to discover new and less invasive treatments for this aggressive benign tumor.
Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, swallowing, and tasting functions remains one of the major challenges in head and neck oncologic surgery. Through decades of evolution in reconstructive principles and techniques, microvascular soft tissue free flaps have evolved as the reconstructive technique of choice following extirpation of malignant neoplasms. However, these free flaps, made up of skin, subcutaneous adipose tissue and fascia, do not allow for the structural restoration of muscular-like tissues and functional restoration of the tongue (innervation, tasting). Additionally, harvesting these flaps will always result in donor site morbidity that will cause some degrees of local pain, edema, limb weakness, and scar formation. Therefore, novel approaches are imperatively needed to generate tissue engineering/regenerative medicine (TE/RM) product for tongue myomucosal regeneration following the surgical ablation of oral cancers. In recent years, there is growing enthusiasm for the use of mesenchymal stem cells (MSCs) for generation of TE/RM products to facilitate repair/regeneration of damaged muscles. We have recently isolated a subpopulation of MSCs from human gingival tissues (GMSCs), which exhibit potent multipotent differentiation and immunomodulatory/anti-inflammatory capabilities. This work will test the hypothesis that generation of GMSC-based TE/RM products represents a promising approach to promote myomucosal regeneration of the tongue and has the potential for clinical application. Specifically, we will generate GMSC-laden porcine small intestine submucosa extracellular matrix (SIS-ECM) constructs and optimize their regenerative potentials in a critical-sized tongue defect model in rats and further explore the potential mechanisms. Accomplishment of this study will provide substantial evidence for the potential clinical application of GMSC-laden SIS/ECM constructs for tongue reconstruction.