A Gingiva-Derived Mesenchymal Stem Cell-Laden Porcine Small Intestinal Submucosa Extracellular Matrix Construct Promotes Myomucosal Regeneration of the Tongue

In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingiva-derived mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction. We developed a rat model of critical-sized myomucosal defect of the tongue that allowed the testing of therapeutic effects of an acellular SIS-ECM construct versus a GMSC/SIS-ECM construct on repair and regeneration of the tongue defect. We showed that the GMSC/SIS-ECM construct engrafted at the host recipient site, promoted soft tissue healing, and regenerated the muscular layer, compared to the SIS-ECM alone or nontreated defect controls. Furthermore, our results revealed that transplantation of the GMSC/SIS-ECM construct significantly increased the expression of several myogenic transcriptional factors and simultaneously suppressed the expression of type I collagen at the wounded area of the tongue. These compelling findings suggest that, unlike the tongue contracture and fibrosis of the nontreated defect group, transplantation of the combinatorial GMSC/SIS-ECM constructs accelerates wound healing and muscle regeneration and maintains the overall tongue shape, possibly by both enhancing the function of endogenous skeletal progenitor cells and suppressing fibrosis. Together, our findings indicate that GMSC/SIS-ECM potentially served as a myomucosal graft for tongue reconstruction postsurgery of head and neck cancer. © Copyright 2017, Mary Ann Liebert, Inc

Oral Rehabilitation of Patients Sustaining Orofacial Injuries: The UPenn Initiative

Tissue injuries in the oral and maxillofacial structures secondary to trauma, warfare, ablative cancer, and benign tumor surgery result in significant losses of speech, masticatory and swallowing functions, aesthetic deformities, and overall psychological stressors and compromise. Optimal oral rehabilitation remains a formidable challenge and an unmet clinical need due to the influence of multiple factors related to the physiologic limitations of tissue repair, the lack of site and function-specific donor tissues and constructs, and an integrated team of multidisciplinary professionals. The advancements in stem cell biology, biomaterial science, and tissue engineering technologies, particularly the 3-dimensional bioprinting technology, together with digital imaging and computer-aided design and manufacturing technologies, have paved the path for personalized/precision regenerative medicine. At the University of Pennsylvania, we have launched the initiative to integrate multidisciplinary health professionals and translational/clinical scientists in medicine, dentistry, stem cell biology, tissue engineering, and regenerative medicine to develop a comprehensive, patient-centered approach for precision and personalized reconstruction, as well as oral rehabilitation of patients sustaining orofacial tissue injuries and defects, especially oral cancer patients

Targeted Inhibition of CD133+ Cells in Oral Cancer Cell Lines

Resistance to treatment and the appearance of secondary tumors in head and neck squamous cell carcinomas (HNSCC) have been attributed to the presence of cells with stem-cell-like properties in the basal layer of the epithelium at the site of the lesion. In this study, we tested the hypothesis that these putative cancer stem cells (CSC) in HNSCC could be specifically targeted and inhibited. We found that 9 of 10 head and neck tumor biopsies contained a subpopulation of cells that expressed CD133, an unusual surface-exposed membrane-spanning glycoprotein associated with CSC. A genetically modified cytolethal distending toxin (Cdt), from the periodontal pathogen Aggregatibacter actinomycetemcomitans , was conjugated to an anti-human CD133 monoclonal antibody (MAb). The Cdt-MAb complex preferentially inhibited the proliferation of CD133+ cells in cultures of established cell lines derived from HNSCC. Inhibition of the CD133+ cells was rate- and dose-dependent. Saturation kinetics indicated that the response to the Cdt-MAb complex was specific. Healthy primary gingival epithelial cells that are native targets of the wild-type Cdt were not affected. Analysis of these data provides a foundation for the future development of new therapies to target CSC in the early treatment of HNSCC. Abbreviations: Cdt, cytolethal distending toxin; CSC, cancer stem cells; HNSCC, head and neck squamous cell carcinoma; MAb, monoclonal antibody. © 2011 International & American Associations for Dental Research

Considerations in the evaluation and management of oral potentially malignant disorders during the COVID-19 pandemic

Aim: The COVID-19 pandemic has resulted in society experiencing unprecedented challenges for health care practitioners and facilities serving at the frontlines of this pandemic. With regard to oral cancer, there is a complete absence of literature regarding the long-term impact of pandemics on patients with oral potentially malignant disorders (OPMDs). The objective of this article is to put forth an institutional multidisciplinary approach for the evaluation and management of OPMDs. Methods: A multidisciplinary approach was put formalized within our institution to risk stratify patients based on need for in-person assessment vs telehealth assessment during the COVID-19 pandemic. Results: With judicious risk stratification of patients based on clinical features of their OPMD and with consideration of ongoing mitigation efforts and regional pandemic impact, providers are able to safely care for their patients. Conclusions: The COVID-19 pandemic has required health care practitioners to make novel decisions that are new to us with development of creative pathways of care that focused on patient safety, mitigation efforts, and clinical management of disease processes. The care of patients with OPMDs requires special considerations especially as patients at high risk for severe COVID-19 illness are also higher risk for the development of OPMDs. © 2020 Wiley Periodicals, Inc

Recent Nuclear Astrophysics Measurements using the TwinSol Separator

Many astrophysical events, such as novae and X-ray bursts, are powered by reactions with radioactive nuclei. Studying the properties of these nuclei in the laboratory can therefore further our understanding of these astrophysical explosions. The TwinSol separator at the University of Notre Dame has recently been used to produce intense (∼106 pps) beams of 17F. In this article, some of the first measurements with these beams are discussed

Particle decay of astrophysically-important \u3csup\u3e19\u3c/sup\u3eNe levels

The 15O(α,γ)19Ne reaction is an important trigger reaction leading to the rapid proton (rp) capture process in X-ray bursts. The primary uncertainty in determining its astrophysical rate is the uncertain α branching ratios of levels near Ex = 4.1 MeV in 19Ne. These states have been populated in a study of the 20Ne(p, d)19Ne reaction, and α branching ratios are reported in this manuscript

Direct neutron capture cross section on Ge 80 and probing shape coexistence in neutron-rich nuclei

Results are presented from the first neutron-transfer measurement on Ge80 using an exotic beam from the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory. Newly measured spins and spectroscopic factors of low-lying states of Ge81 are determined, and the neutron capture cross section on Ge80 was calculated in a direct-semidirect model to provide a more realistic (n,γ) reaction rate for r-process simulations. Furthermore, a region of shape coexistence around N≈50 is confirmed and implications for the magic nature of Ni78 are discussed