Organogenesis of Ectopic Tissue in Lymph Node

淋巴结异位组织的器官发生

• 批准号: 8133503
• 负责人: ERIC LAGASSE
• 金额: $ 70.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133503
• 关键词: 3-Dimensional; Address; Bioreactors; Cells; Choristoma; Cirrhosis; Complex; Data; Development; Disease; Fibrosis; Generations; Hepatic; Hepatocyte; Liver; Liver Failure; Liver diseases; Methods; Organ; Organogenesis; Patients; Reporting; Site; Solutions; Staging; Therapeutic; Tissue Engineering; Tissue Model; Tissues; Transplantation; base; in vivo; lymph nodes; novel; public health relevance

DESCRIPTION (provided by applicant): Our proposal addresses some of the solutions to the development of complex 3- dimensional tissue models and a new paradigm by using lymph node as in vivo bioreactors to grow tissue or organ substitute. Our initial study and prove of concept will be centered around the generation of ectopic liver in lymph nodes for patients suffering end-stage liver diseases. Hepatocyte transplantation has been reported as a possible therapeutic approach for liver disease. However, transplantation has been directed at the liver itself, limiting efficacy in patients with end-stage liver diseases, when cirrhosis and fibrosis are common. In this proposal we demonstrate that the generation of an ectopic liver within lymph nodes is an efficient method to restore hepatic function, highlighting the novel use of this organ as a site for hepatocyte transplantation. Homeostatic expansion of donor hepatocytes in lymph nodes resulted in the rescue of lethal hepatic failure. These data provide the first definitive evidence that a functional ectopic liver can rescue lethal hepatic diseases. Furthermore, with the efficacy of this approach suggests that lymph nodes have therapeutic potential for cell-based transplantation and tissue engineering. Our new paradigm to generate functional liver tissues in lymph nodes will be further applied to other tissues. PUBLIC HEALTH RELEVANCE: Our proposal addresses some of the hurdles confronting the development of complex 3-D tissue models, and provides a new paradigm for tissue modeling, by using lymph nodes as in vivo bioreactors to grow tissue or organ substitutes.

描述（由申请人提供）：我们的提案提出了开发复杂的 3 维组织模型的一些解决方案，以及通过使用淋巴结作为体内生物反应器来生长组织或器官替代品的新范例。我们的初步研究和概念验证将集中在患有终末期肝病的患者的淋巴结中产生异位肝脏。据报道，肝细胞移植是治疗肝病的一种可能的方法。然而，移植针对的是肝脏本身，限制了肝硬化和纤维化常见的终末期肝病患者的疗效。在该提案中，我们证明在淋巴结内生成异位肝脏是恢复肝功能的有效方法，强调了该器官作为肝细胞移植部位的新用途。淋巴结中供体肝细胞的稳态扩张导致致命性肝衰竭的挽救。这些数据提供了第一个明确的证据，证明功能性异位肝脏可以挽救致命的肝脏疾病。此外，这种方法的功效表明淋巴结具有基于细胞的移植和组织工程的治疗潜力。我们在淋巴结中生成功能性肝组织的新范例将进一步应用于其他组织。 公共健康相关性：我们的提案解决了复杂 3D 组织模型开发所面临的一些障碍，并通过使用淋巴结作为体内生物反应器来生长组织或器官替代品，为组织建模提供了新的范例。