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

摘要 哈钦森-吉尔福德早衰症(HGPS)是一种导致早产和早衰的遗传性疾病。 在生理衰老过程中，孕激素的积累也会发生。我们的胎教项目旨在 优化由患者来源的成纤维细胞(FBS)生成的仿生HGPS芯片上系统，平滑 肌肉细胞(SMC)和内皮细胞(ECs)，允许应用相关的循环拉伸来执行 “临床试验”或告知HGPS患者的临床试验设计。考虑到独特的微重力环境 国际空间站-国家实验室(ISS-NL)的一部分，它之前已经被证明构成了各种 对血管细胞表型的负面影响，这一补充进一步旨在开发一种方法学来 通过以下方式实现多层、高细胞密度、生物反应器集成的血管管道的空间生物打印 Techshot在国际空间站-国家实验室(ISS-NL)的生物制造能力(BFF)，以及 研究微重力条件下的血管早衰。圆满完成拟议补编 该项目将在多个方面具有变革性。首先，它将通过以下方式演示一种独特的太空中最好的朋友工具 使用新的生物油墨配方对一种以前没有做过的新组织类型进行生物打印。然而，当我们 目标血管生物打印，我们预计该技术也适用于许多其他类型的组织 必要的修改。其次，生物学研究将使太空和地球上的生命受益。血管 老龄化是一个影响数百万人的紧迫医学问题，也是一个潜在的重大病理问题 为宇航员，特别是未来深空任务的表现者。根据我们的假设，血管 用HGPS细胞生物打印的管道将表现出与病理相关的早衰表型，即 受空间微重力环境的影响比那些拥有健康细胞和 在地球上，我们期待着掌握更多关于 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及以后的预防和治疗干预措施。

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.