Deposition of data from ground and flight samples for sarcopenia MPS system

为肌少症 MPS 系统沉积地面和飞行样本数据

• 批准号: 10434403
• 负责人: Siobhan Malany
• 金额: $ 7.63万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10434403
• 关键词: 3-Dimensional; Address; Adult; Age; Aging; Applications Grants; Area; Astronauts; Atrophic; Biological; Cells; Cellular Stress; Computer software; DNA Damage; Data; Devices; Disease model; Drug Delivery Systems; Elderly; Electrodes; Engineering; Extracellular Matrix; Florida; Functional disorder; Gene Expression; Health Care Costs; Human; Individual; International; Lab-On-A-Chips; Laboratories; Liquid substance; Microgravity; Modeling; Muscle; Muscle Cells; Muscle Fibers; Muscular Atrophy; Natural Products; Older Population; Optics; Pharmaceutical Preparations; Pharmacy facility; Phenotype; Physiological; Population; Property; Quality of life; Research; Research Institute; Research Personnel; Sampling; Skeletal Muscle; Space Flight; System; Testing; Therapeutic; Time; Tissue Donors; Toxicology; Translational Research; United States National Institutes of Health; Universities; age related; aged; cell growth; clinical development; clinically relevant; college; data submission; detection platform; drug efficacy; electric field; experimental study; human tissue; improved; microphysiology system; miniaturize; mitochondrial dysfunction; muscle degeneration; muscle form; muscle strength; next generation; parent grant; physiologic stressor; prevent; response; sarcopenia; sedentary; senescence; skeletal muscle wasting; space station; therapeutic development; translational research program; volunteer

PARENT GRANT PROJECT SUMMARY This grant application, in response to RFA-TR-18-001 “NIH-CASIS Coordinated Microphysiological Systems Program for Translational Research in Space”, proposes an outstanding collaborative effort among investigators at the University of Florida, College of Pharmacy and Engineering and AdventHealth Translational Research Institute. Astronauts suffer from muscle degeneration after prolonged spaceflight. These effects are largely reversible; however, the intrinsic changes in skeletal muscle observed with age such as DNA damage, cellular stress, mitochondrial dysfunction and senescence are likely to overlap with cellular mechanisms induced in microgravity. Thus, studies in microgravity using human tissue to model disease conditions may greatly contribute to development of clinically relevant approaches to address muscle wasting in the elderly referred to as sarcopenia. The number of elderly individuals over the age of 60 is growing at an unprecedented rate from ~11% of the global population today to ~21% by 2050. Therapeutic options to treat sarcopenia are non-existent in part because of an incomplete understanding of the mechanisms controlling age-related skeletal muscle dysfunction. Our team has developed a 2D millifluidic lab-on-a-chip system to study human skeletal muscle cell growth and gene expression changes in microgravity. We have established culture conditions for primary human myocytes isolated from young, healthy and older, sedentary volunteers and have biological data indicating that the cells retain the phenotype of the donor tissue. Furthermore, we have fabricated a flight ready chip with multiple culture chambers. For this proposal, we plan to develop a microphysiological (MPS) 3D system and incorporate electrodes into the chip. We will determine electric field strength distribution using COMSOL modeling and optimize conditions for electrically stimulating muscle myocytes embedded in a native extracellular matrix. Our MPS will be integrated into a remote controlled, fully automated laboratory complete with a fluid handling system, an optical detection system to record contraction, and a software platform for near real-time control of the experiment on the ISS housed in the TangoLab experimental flight facility. On a subsequent flight, we propose to test natural products with anti-atrophy properties in the validated MPS. Drug delivery to the muscle cultures will be facilitated via the addition of an administration port capable of delivering multiple drug dilutions. Our next generation MPS system stands to be a leader in miniaturized lab disease modeling to study pathophysiological changes in muscle tissue induced in microgravity intended to advance drug efficacy and toxicological testing to treat muscle wasting.

家长助学金项目摘要 这项赠款申请，响应RFA-TR-18-001“NIH-CASIS协调 用于空间翻译研究的微生理系统计划“，提出了一种 佛罗里达大学学院研究人员之间出色的合作努力 药学与工程与AdventHealth翻译研究所。宇航员 在长时间的太空飞行后肌肉退化。这些影响主要是 可逆的；然而，骨骼肌随年龄增长而观察到的内在变化，如DNA 损伤、细胞应激、线粒体功能障碍和衰老可能是重叠的 在微重力下诱导的细胞机制。因此，使用人类进行微重力研究 以组织为模型的疾病状况可能极大地有助于临床相关疾病的发展 解决老年人肌肉萎缩的方法称为骨质疏松症。这个 60岁以上的老年人数量正以前所未有的速度增长 到2050年，全球人口的比例将从目前的11%增加到21%。治疗石棺减少症的治疗选择 不存在的部分原因是对机制的不完全理解 控制年龄相关性骨骼肌功能障碍。我们的团队已经开发出一种2D毫秒流 用于研究人骨骼肌细胞生长和基因表达的芯片实验室系统 微重力的变化。我们已经建立了原代人心肌细胞的培养条件。 从年轻、健康和年长的久坐不动的志愿者中分离出来，并有生物学数据 这表明细胞保留了供体组织的表型。此外，我们还拥有 制造了一个带有多个培养室的飞行准备芯片。对于这项建议，我们计划 开发微生理(MPS)3D系统，并将电极集成到芯片中。我们 将使用COMSOL建模和优化来确定电场强度分布 电刺激肌细胞包埋于天然细胞外的条件 矩阵。我们的MPS将集成到一个远程控制的全自动化实验室 配有液体处理系统、记录收缩的光学探测系统，以及 一个软件平台，用于近乎实时地控制国际空间站上的实验 TangoLab实验飞行设施。在接下来的飞行中，我们建议测试自然 经过验证的MPS中具有抗萎缩特性的产品。肌肉给药 文化将通过增加一个管理端口来促进，该管理端口能够提供 药物稀释。我们的下一代MPS系统将成为小型化实验室的领先者 疾病模型研究大鼠肌肉组织的病理生理变化 微重力旨在提高治疗肌肉萎缩的药物疗效和毒理学测试。