Interplay Between Stem Cells and Inflammation in Benign Prostatic Hyperplasia

项目名称 良性前列腺增生中干细胞与炎症的相互作用 项目摘要 良性前列腺增生的病因与症状 (BPH)需要一种新的方法来了解其细胞病因。我们正在建立一个临床标注的 新鲜的组织储存库，用于询问细胞特异性波动和分子特征。小鼠中的证据 而人类的研究表明，雄激素非依赖性干细胞在基底上皮中富集， 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的增加是否 或其后代是BPH的病因。此外，人前列腺体积与慢性前列腺增生直接相关。 在小鼠模型中，前列腺上皮干细胞被炎症激活。因此，委员会认为， 这项研究将建立一个新鲜的组织人类BPH储存库，将用于调查假设， 炎症与人BPH中的干细胞活性相关。开创性的研究寻找起源于 前列腺癌最近产生了用于收集和功能表征的标准化方案 从人类前列腺干细胞，创造了一个机会，解决炎症之间的联系， 细胞和上皮干细胞活性。为了达到这个目的，我利用了我部门的高风险病人 体积，以优化新鲜组织收集、干细胞和炎性细胞鉴定的方案， 流式细胞术和干细胞在3D类器官培养物中的连续传代。初步数据显示， 这是我的K奖假设的自然发展， 调节前列腺上皮的自我更新和分化。这项研究计划意义重大，因为它 为临床观察提供了一种细胞病因学，即前列腺体积大的患者显示高 炎症和抗雄激素治疗抵抗，它是创新的，在其发展的一个新的 使用流式细胞术和3D类器官的最新技术进展的人类前列腺生物储存库 文化人体组织储存库的建立将为人类组织研究提供资源和初步数据。 R01申请2年内获得早期研究者身份。

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.