Interplay Between Stem Cells and Inflammation in Benign Prostatic Hyperplasia

良性前列腺增生中干细胞与炎症之间的相互作用

• 批准号: 9166471
• 负责人: Douglas William Strand
• 金额: $ 8.1万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-25 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9166471
• 关键词: 5 Alpha-Reductase Inhibitor; Address; Adverse effects; Age; Aging; Androgens; Animals; Antiandrogen Therapy; B-Lymphocytes; Basal Cell; Benign Prostatic Hypertrophy; Castration; Cd68; Cell Proliferation; Cells; Chronic; Clinical; Clinical Data; Collaborations; Communities; Data; Development; Epithelial; Epithelial Cells; Epithelium; Etiology; Flow Cytometry; Frequencies; Fresh Tissue; Future; Goals; Growth; Harvest; Health; Human; Immunohistochemistry; Incidence; Inflammation; Inflammatory; K-Series Research Career Programs; Laboratories; Leukocytes; Link; Malignant neoplasm of prostate; Mesenchyme; Metabolism; Molecular; Molecular Profiling; Morbidity - disease rate; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Natural regeneration; Nickel; Operative Surgical Procedures; Organoids; PTPRC gene; Patient observation; Patients; Pharmaceutical Preparations; Population; Proliferating; Prostate; Protocols documentation; Research; Research Personnel; Research Proposals; Resistance; Resources; Risk; Sampling; Serial Passage; Severities; Site; Specimen; Staging; Stem cells; Strategic Planning; Symptoms; T-Lymphocyte; Testing; Therapeutic; Tissue Banks; Tissues; Translational Research; biobank; cell type; experience; human disease; human stem cells; human tissue; innovation; lower urinary tract symptoms; macrophage; male health; men; mouse model; neoplastic cell; new therapeutic target; novel strategies; public health relevance; repository; self-renewal; stem; stem cell population; targeted treatment; therapy development; therapy resistant; tissue processing; tissue regeneration

Project title Interplay Between Stem Cells and Inflammation in Benign Prostatic Hyperplasia Project summary The development of therapies that target the causes rather than the symptoms of benign prostatic hyperplasia (BPH) requires a novel approach to understanding its cellular etiology. We are building a clinically annotated fresh tissue repository for interrogating cell-specific fluctuations and molecular signatures. Evidence in mice and humans demonstrate that androgen-independent stem cells are enriched in the basal epithelium, which is also the site of the majority of proliferating cells in BPH tissue. It is unclear whether increases in stem cells or their progeny are causative in BPH. In addition, human prostate volume is directly correlated with chronic inflammation, and prostate epithelial stem cells are activated by inflammation in mouse models. Accordingly, this study will build a fresh tissue human BPH repository that will be used to investigate the hypothesis that inflammation is correlated with stem cell activity in human BPH. Pioneering studies looking for a cell of origin in prostate cancer have recently produced standardized protocols for harvesting and functionally characterizing stem cells from human prostate, creating an opportunity to address the connections between inflammatory cells and epithelial stem activity in BPH. Towards this end, I have leveraged my department's high patient volume to optimize protocols for fresh tissue collection, stem and inflammatory cell identification by multicolor flow cytometry, and serial passaging of stem cells in 3D organoid culture. The preliminary data has been generated solely in my new laboratory and is a natural progression of my K award hypothesis that metabolism regulates prostate epithelial self-renewal and differentiation. This research proposal is significant because it provides a cellular etiology for the clinical observation that patients with a large prostate volume display high inflammation and are resistant to anti-androgen therapy, and it is innovative in its development of a fresh human prostate biorepository for use of the latest technical advances in flow cytometry and 3D organoid culture. The development of a human tissue repository will provide the resources and preliminary data for an R01 application with Early Stage Investigator status in 2 years.

项目标题 干细胞之间的相互作用与良性前列腺增生的炎症 项目摘要 靶向原因而不是良性前列腺增生症状的疗法的发展 （BPH）需要一种新的方法来理解其细胞病因。我们正在建立一个临床注释 新鲜组织存储库，用于询问细胞特异性波动和分子特征。小鼠的证据 人类证明，雄激素非依赖性干细胞富集在基底上皮中，这是 也是BPH组织中大多数增殖细胞的部位。目前尚不清楚干细胞中是否增加 或他们的后代在BPH中是病因。此外，人前列腺体积与慢性直接相关 在小鼠模型中，炎症和前列腺上皮干细胞通过炎症激活。因此， 这项研究将建立一个新鲜的组织人BPH存储库，该存储库将用于研究以下假设。 炎症与人BPH中的干细胞活性相关。开创性研究，寻找原始细胞 前列腺癌最近生产了用于收获和功能表征的标准化方案 人类前列腺干细胞，创造了解决炎症之间联系的机会 BPH中的细胞和上皮茎活性。为此，我利用了我部门的高病人 数量优化新鲜组织收集，茎和炎症细胞鉴定的方案 流式细胞仪和3D器官培养中干细胞的系列传递。初步数据已经 仅在我的新实验室中产生，这是我的K奖假设的自然发展，该假设是代谢 调节前列腺上皮自我更新和分化。这项研究建议很重要，因为它 为临床观察提供了一个细胞病因，即前列腺量较大的患者显示高 炎症，对抗雄激素疗法有抵抗力，并且在开发新鲜方面具有创新性 人类前列腺生物座席使用流式细胞仪和3D器官的最新技术进步 文化。人体组织存储库的开发将为A提供资源和初步数据 R01在2年内具有早期调查员地位的应用。