Salivary gland repair and regeneration via Schwann cell-nerve interactions

通过雪旺细胞-神经相互作用进行唾液腺修复和再生

基本信息

批准号：
8514569
负责人：
Sarah Monica Knox
金额：
$ 26.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-20 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8514569
关键词：
Acinus organ component Address Adult Aftercare Apoptotic Autologous Binding Biochemical Biological Assay Biopsy Cell Adhesion Cell Communication Cell Survival Coculture Techniques Data Development Embryo Engineering Epithelial Epithelium Functional disorder Gamma Rays Genetic Gland Goals Head and Neck Cancer Human Imaging Techniques Immunofluorescence Immunologic Injury Investigation Knockout Mice Maintenance Measures Membrane Methods Modeling Mus Myocardium Natural regeneration Nerve Neuregulin 1 Neurons Oral health Outcome Patients Primates Quality of life Radiation Radiation therapy Recombinants Rodent Salivary Salivary Glands Sampling Schwann Cells Sjogren&apos s Syndrome Small Interfering RNA Spinal cord injury Stem cell transplant Stem cells Structure of parasympathetic ganglion Submandibular gland Supporting Cell Testing Time Tissue Survival Tissues Transplantation Viral Western Blotting fluorescence imaging forging functional restoration gain of function gene therapy in vivo in vivo Model indexing irradiation loss of function mouse model nerve supply neuronal survival neutralizing antibody novel novel strategies overexpression radiation effect regenerative repaired research study restoration saliva secretion stem synaptogenesis tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Salivary gland dysfunction occurs as a result of pathological injury after radiotherapy for head and neck cancer and significantly compromises the oral health and quality of life of patients. Salivary function and regeneration, as well as the maintenance of epithelial progenitor cells, is dependent on parasympathetic innervation: regeneration only occurs if parasympathetic input is maintained. Current efforts to regenerate salivary tissue and restore function do not address the need to repair parasympathetic innervation. Therefore, in this application we propose to restore salivary function by re-establishing the nerve supply through the use of Schwann cells. Schwann cells are essential for neuronal function, survival and regeneration, and maintaining tissue innervation. We hypothesize that maintaining Schwann cells after radiation, or transplanting autologous Schwann cells into radiation-damaged salivary glands, will enhance neuronal input and promote tissue regeneration. Thus, the Specific Aims of this project are to: 1) Determine the impact of gamma radiation on Schwann cell-neuronal cell interactions; 2) Identify the effects of Neuregulin-1 produced by the nerves on Schwann cell and neuronal survival, nerve function, and epithelial regeneration after irradiation; and 3) Determine the ability of Schwann cells to restore salivary function after irradiation. These aims will be achieved using embryonic ex vivo and adult mouse in vivo models of irradiation in the submandibular gland in conjunction with genetic, biochemical, immunochemical, and fluorescence imaging techniques. Importantly, biopsies from irradiated human glands will be analyzed in parallel. Our investigation will provide sufficient proof-of-principle to support the development of this regenerative strategy in human studies and facillitate our understanding of how radiation influences salivary gland regeneration and repair.

描述（由申请人提供）：唾液腺功能障碍是由于放射疗法治疗头颈癌后病理损伤而导致的，并显着损害了患者的口腔健康和生活质量。唾液功能和再生以及上皮祖细胞的维持，取决于副交感神经：仅当保持副交感输入时才发生再生。当前的唾液组织和恢复功能的努力并不能满足修复副交感神经的需求。因此，在此应用程序中，我们建议通过使用Schwann细胞重新建立神经供应来恢复唾液功能。 Schwann细胞对于神经元功能，生存和再生以及维持组织神经是必不可少的。我们假设在辐射后保持雪旺细胞，或将自体雪水细胞移植到受辐射受损的唾液腺中，将增强神经元输入并促进组织再生。因此，该项目的具体目的是：1）确定伽马辐射对Schwann细胞神经元细胞相互作用的影响； 2）确定神经产生的神经蛋白-1对辐射后神经元细胞和神经元存活，神经功能和上皮再生的影响； 3）确定施旺恩细胞在照射后恢复唾液功能的能力。使用遗传，生化，免疫化学和荧光成像技术结合使用胚胎的体内和成年小鼠在体内辐射模型中，将实现这些目标。重要的是，将同时分析来自受辐照的人腺的活检。我们的调查将提供足够的原则证明，以支持人类研究中这种再生策略的发展，并促进我们对辐射如何影响唾液腺再生和修复的理解。