权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Electrical Stimulation of Human Myocytes in Microgravity: An In Vitro Model to Evaluate Therapeutics to Counteract Muscle Wasting

微重力下人体心肌细胞的电刺激：评估对抗肌肉萎缩治疗方法的体外模型

基本信息

批准号：
10262954
负责人：
Siobhan Malany
金额：
$ 48.32万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
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/10262954
关键词：
Address Adult Age Aging Applications Grants Area Astronauts Athletic Atrophic Attenuated Biological Biological Models Biomedical Engineering Cells Cellular Stress Collaborations Computer software Contracts DNA Damage Data Detection Development Devices Diabetes Mellitus Disease Progression Disease model Drug Delivery Systems Drug Screening Elderly Electric Stimulation Electrodes Environment Exposure to Extracellular Matrix FDA approved Florida Functional disorder Gene Expression Goals Health Care Costs Hospitals Human Hydrogels Hypogravity In Vitro Individual Institutes International Intervention Island Lab-On-A-Chips Laboratories Liquid substance Manuals Medical Metabolism Microgravity Modeling Molecular Monitor Muscle Muscle Cells Muscle Fibers Muscular Atrophy Natural Products Older Population Optics Pathway interactions Pharmaceutical Preparations Pharmacology Study Phase Phenotype Physical Performance Physiological Planet Earth Population Process Property Protocols documentation Pulse Rates Quality of life Research Research Institute Research Personnel Sampling Skeletal Muscle Space Flight Specialist System Technology Testing Therapeutic Time Tissue Donors Tissue Engineering Tissues Toxicology Translational Research United States National Institutes of Health Universities age related age-related muscle loss aged cell growth cell type clinical development clinically relevant design detection platform drug candidate drug discovery drug efficacy electric field experimental study human tissue improved in vitro Model microphysiology system miniaturize mitochondrial dysfunction multidisciplinary muscle aging muscle degeneration muscle form muscle strength next generation novel therapeutics physiologic model prevent response safety assessment sarcopenia sedentary senescence simulation skeletal muscle wasting space station systems research therapeutic development therapeutic evaluation transcriptome translational research program volunteer

项目摘要

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 Sanford Burnham Prebys Medical Discovery Institute, SpacePharma, INC, Florida Hospital Translational Research Institute for Metabolism and Diabetes, the University of Florida Department of Biomedical Engineering and Space Technology and Advanced Research Systems (STaARS). 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 relatively non-existent in part because of an incomplete understanding of the mechanisms controlling age-related skeletal muscle dysfunction. Our team has been focused on developing a 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 incorporate electrodes into the chip and determine electric field strength distribution by simulation to optimize conditions for electrically stimulating muscle myocytes embedded in a native mimicking extracellular matrix. Our lab-on-a- chip will be integrated into a remote controlled, fully automated laboratory solution 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 STaARS-1 experimental flight facility. On a subsequent flight, we propose to test natural products with anti-atrophy properties in the validated lab-on-a-chip system. 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 lab-on-a-chip 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 of therapeutics to elevate the burden of muscle wasting.

项目总结

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells.

DOI：
10.1111/acel.13650
发表时间：
2022-07
期刊：
Aging cell
影响因子：
7.8
作者：
通讯作者：

Validation of Human Skeletal Muscle Tissue Chip Autonomous Platform to Model Age-Related Muscle Wasting in Microgravity.

验证人体骨骼肌组织芯片自主平台模拟微重力下与年龄相关的肌肉萎缩。

DOI：
10.21203/rs.3.rs-2631490/v1
发表时间：
2023
期刊：
Research square
影响因子：
0
作者：
Parafati,Maddalena;Giza,Shelby;Shenoy,Tushar;Mojica-Santiago,Jorge;Hopf,Meghan;Malany,Legrand;Platt,Don;Kuehl,Paul;Moore,Isabel;Jacobs,Zachary;Barnett,Gentry;Schmidt,Christine;McLamb,William;Coen,Paul;Clements,Twyman;Malany,
通讯作者：
Malany,

Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight.

人骨骼肌组织芯片自主有效载荷揭示了由于太空飞行而引起的纤维类型和代谢基因表达的变化。

DOI：
10.1038/s41526-023-00322-y
发表时间：
2023-09-15
期刊：
NPJ MICROGRAVITY
影响因子：
5.1
作者：
Parafati, Maddalena;Giza, Shelby;Shenoy, Tushar S.;Mojica-Santiago, Jorge A.;Hopf, Meghan;Malany, Legrand K.;Platt, Don;Moore, Isabel;Jacobs, Zachary A.;Kuehl, Paul;Rexroat, JasHainanon;Barnett, Gentry;Schmidt, Christine E.;McLamb, William T.;Clements, Twyman;Coen, Paul M.;Malany, Siobhan
通讯作者：
Malany, Siobhan