Defining mechanisms driving salivary gland regeneration

定义驱动唾液腺再生的机制

• 批准号: 10655462
• 负责人: Sarah Monica Knox
• 金额: $ 96.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655462
• 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; body system; cholinergic; craniofacial; craniofacial tissue; gland development; human tissue; improved; novel; organ regeneration; organ repair; progenitor; programs; regenerative approach; repaired; stem cell therapy; 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.

项目摘要/摘要 开发基于干细胞的治疗疾病和恢复器官功能的疗法导致了关键 需要在颅面组织中鉴定内源性干细胞及其调节剂。我们已经很重要 进入唾液腺的解密干细胞身份和调节（一种颅面器官系统） 受到慢性疾病（例如衰老，自身免疫性，癌症）的深刻影响，有症状的影响很少 治疗和没有长期恢复性疗法。但是，尽管该领域的进展，我们仍然非常 在理解驱动器官修复和再生的机制的早期阶段。因此，基于我们的 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）如何神经 控制器官稳态和再生？ （3）衰老如何影响唾液干细胞？最后，（4） 如何创建唾液腺建筑？我们将使用的结合来回答这些问题 小鼠和人体组织中的发育和再生方法以及分子 生化，成像和细胞生物学测定。这里的结果将发现新颖的细胞和分子 开发基于干细胞的疗法所需的机制，以逆转这些损害和 其他器官系统。