"Clinical Trials" on a Premature Vascular Aging-on-a-Chip Model

血管过早老化芯片模型的“临床试验”

• 批准号: 10691727
• 负责人: Yu Shrike Zhang
• 金额: $ 13.53万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10691727
• 关键词: Adult; Affect; Aging; Astronauts; Biological; Biomimetics; Bioreactors; Blood Vessels; Cell Density; Cells; Child; Clinical Trials; Clinical Trials Design; Developmental Biology; Endothelial Cells; Environment; Fibroblasts; Formulation; Future; Genetic Diseases; International; Knowledge; Laboratory Study; Life; Medical; Methodology; Microgravity; Mission; Modeling; Modification; Pathologic; Patients; Periodicity; Persons; Phenotype; Physiological; Planet Earth; Premature aging syndrome; Progeria; Smooth Muscle Myocytes; Stretching; Syndrome; System; Technology; Therapeutic Intervention; Tissues; biofabrication; bioink; bioprinting; grasp; premature; preventive intervention; space station

Abstract Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder that results in premature and accelerated aging, while accumulation of progerin also occurs during physiological aging. Our paratal project seeks to optimize a biomimetic HGPS-on-a-chip system generated with patient-derived fibroblasts (FBs), smooth muscle cells (SMCs), and endothelial cells (ECs) that allow application of relevant cyclic stretch for performing ‘clinical trials’ or informing clinical trial designs for HGPS patients. Given the unique microgravity environment of the International Space Station-National Lab (ISS-NL), which has been shown before to pose various negative effects on vascular cell phenotypes, this supplement further aims at developing a methodology to enable in-space bioprinting of multi-layered, high-cell-density, bioreactor-integrated vascular conduits through Techshot’s BioFabrication Faclity (BFF) at the International Space Station-National Laboratory (ISS-NL), and studying premature vascular aging under microgravity. Successful completion of the proposed supplement project will be transformative in multiple aspects. First, it will demonstrate a unique in-space BFF utility through the use of new bioink formulations for the bioprinting of a new tissue type not previously done. Yet, while we target vascular bioprinting, we anticipate that the technology is applicable to many other tissue types with necessary modifications. Second, the biological study will benefit life both in space and on Earth. Vascular aging is a pressing medical problem that affects millions of people, and is potentially also a major pathological manifestation for astronauts especially for future deep-space missions. Under our hypothesis that vascular conduits bioprinted with HGPS cells will manifest a pathologically relevant premature aging phenotype that is more severely affected by the space microgravity environment than those with healthy cells and those on Earth, we anticipate grasping additional fundamental knowledge regarding the underlying mechanisms of vascular aging in both children and adults in association with developmental biology, which will further instruct prevention and therapeutic interventions in the future in HGPS and beyond.

抽象的 哈钦森-吉尔福德早衰综合症 (HGPS) 是一种遗传性疾病，会导致早衰和加速 衰老，而早老素的积累也会发生在生理衰老过程中。 优化由患者来源的成纤维细胞 (FB) 生成的仿生 HGPS 芯片系统，平滑 肌肉细胞 (SMC) 和内皮细胞 (EC) 允许应用相关的循环拉伸来执行 鉴于独特的微重力环境，“临床试验”或为 HGPS 患者提供临床试验设计信息。 国际空间站国家实验室（ISS-NL）的，之前已被证明可以提出各种 对血管细胞表型的负面影响，该补充品进一步旨在开发一种方法 通过以下方式实现多层、高细胞密度、生物反应器集成血管导管的空间生物打印 Techshot 位于国际空间站国家实验室 (ISS-NL) 的生物制造设施 (BFF)，以及 研究微重力下的血管过早老化。成功完成拟议的补充。 该项目将在多个方面带来变革，首先，它将通过展示独特的太空 BFF 实用程序。 使用新的生物墨水配方来生物打印以前从未做过的新组织类型。 目标血管生物打印，我们预计该技术适用于许多其他组织类型 其次，生物学研究将有益于太空和地球上的生命。 衰老是影响数百万人的一个紧迫的医学问题，也可能是一个主要的病理学问题 根据我们的假设，血管是宇航员尤其是未来深空任务的表现。 用 HGPS 细胞生物打印的导管将表现出病理相关的过早衰老表型，即 与健康细胞和在太空中的细胞相比，受太空微重力环境的影响更严重 地球，我们期望掌握有关基本机制的更多基础知识 儿童和成人的血管老化与发育生物学相关，这将进一步指导 未来 HGPS 及其他领域的预防和治疗干预。