Defining mechanisms driving salivary gland regeneration

定义驱动唾液腺再生的机制

• 批准号: 10063228
• 负责人: Sarah Monica Knox
• 金额: $ 5.13万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2020-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10063228
• 关键词: Affect; Aging; Architecture; Autoimmunity; Automobile Driving; Biochemical; Biological Assay; Cell Therapy; Cells; Chronic Disease; Development; Disease; Goals; Homeostasis; Image; Laboratories; Maintenance; Malignant Neoplasms; Molecular; Mus; Natural regeneration; Nerve; Organ; Outcome; Quality of life; Regulation; Role; Salivary; Salivary Glands; Stem Cell Development; Therapeutic; base; body system; cholinergic; craniofacial; craniofacial tissue; gland development; human tissue; improved; novel; progenitor; programs; regenerative; repaired; stem cells; symptom treatment

Project Summary/Abstract The development of stem cell-based therapies for curing disease and restoring organ function has led to a critical need to identify endogenous stem cells and their regulators in craniofacial tissues. We have made significant inroads into deciphering stem cell identity and regulation in the salivary gland, a craniofacial organ system profoundly affected by chronic diseases (e.g., aging, autoimmunity, cancer) for which there are few symptomatic treatments and no long-term restorative therapies. However, despite progress in the field, we are still very much in the early stages of understanding the mechanisms driving organ repair and regeneration. Thus, based our previous studies revealing the identity and function of salivary progenitors and novel roles of cholinergic nerves in morphogenic and renewal programs, we seek to elucidate the mechanisms driving salivary gland regeneration by exploring 4 significant questions: (1) How do salivary stem cells enable organ renewal? (2) How do nerves control organ homeostasis and regeneration? (3) How does aging impact salivary stem cells? And finally, (4) How is salivary gland architecture created? We will answer these questions using a combination of developmental and regenerative approaches in mice and human tissue together with a bevy of molecular, biochemical, imaging and cell biological assays. Outcomes here will uncover novel cellular and molecular mechanisms required for the development of stem cell based therapeutics for reversing damage in these and other organ systems.

项目概要/摘要 用于治疗疾病和恢复器官功能的干细胞疗法的发展导致了一个关键的问题 需要识别颅面组织中的内源性干细胞及其调节因子。我们已经做出了重大的 破译唾液腺（颅面器官系统）中的干细胞身份和调节取得进展 深受慢性疾病（例如衰老、自身免疫、癌症）影响，而这些疾病几乎没有症状 治疗，并且没有长期的恢复疗法。然而，尽管该领域取得了进展，但我们仍然 处于了解驱动器官修复和再生机制的早期阶段。因此，根据我们的 先前的研究揭示了唾液祖细胞的身份和功能以及胆碱能神经的新作用 在形态发生和更新计划中，我们试图阐明驱动唾液腺再生的机制 通过探索 4 个重要问题：（1）唾液干细胞如何实现器官更新？ (2)神经如何 控制器官稳态和再生？ (3) 衰老如何影响唾液干细胞？最后，(4) 唾液腺结构是如何形成的？我们将结合使用以下方法来回答这些问题 小鼠和人体组织的发育和再生方法以及一系列分子、 生化、成像和细胞生物学测定。这里的结果将揭示新的细胞和分子 开发基于干细胞的疗法以逆转这些损伤所需的机制 其他器官系统。