CAREER: Engineering Autonomic Control of Cardiac Tissues

职业：心脏组织的自主控制工程

• 批准号: 2237898
• 负责人: Tracy Hookway
• 金额: $ 50万
• 依托单位: SUNY at Binghamton
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2237898&HistoricalAwards=false
• 关键词: CAREER; Engineering; Autonomic; Control; Cardiac

The human heart is a critical organ that is responsible for pumping blood to the rest of the body. This pump is able to speed up or slow down to ensure enough blood is carried throughout our bodies during times of activity or during times of rest. The heart is able to achieve this variation in pumping rate through control by the nervous system. Neurons send signals to the heart to change the beat rate and help make sure the heart beats in unison. This Faculty Early Career Development (CAREER) project supports fundamental research to understand how neurons connect to the heart and improve heart function. This research will be achieved by using stem cells in three-dimensional engineered structures to examine how the neurons connect to the heart cells and how the electrical stimulus from the neurons improves beating heart function. Results will help advance knowledge of heart biology, will promote engineering solutions for potential future therapies, and can be used as a drug screening platform. This project is fully integrated with community outreach in the Southern Tier of NY. which is demonstrated through the development of biomedical engineering teaching modules for high school classrooms in local rural communities.The investigator’s long-term career goal is to become a scientific leader in the fields of stem cell and tissue engineering with a specific focus on cardiovascular tissue models and biomanufacturing. Towards this goal, the goal of this CAREER project is to interrogate the role of autonomic neural stimulation on the function of engineered cardiac tissues in vitro. A detailed understanding of the multicellular interactions that occur in the heart is a necessary, but challenging, aspect to improve the performance of engineered cardiac models. The research and education plan is organized under 3 separate objectives. The first objective is to engineer heterotypic multicellular models to measure the effects of autonomic innervation on cardiac contractile behavior and cellular composition. To achieve this, pluripotent stem cells will be differentiated into sympathetic and parasympathetic neurons. These neuronal cell populations will be mixed with cardiomyocytes at different developmental stages to investigate their influence over beat rate, contraction force, and calcium handling kinetics. The second objective is to develop a variable frequency electrical stimulation bioreactor to mimic the signals that the cardiomyocytes receive from the autonomic neurons. Cardiac tissues will be cultured under variable electrical stimulation and their contractile properties will be compared directly to innervated and non-innervated tissues to determine if variable electrical stimulation improves cardiac tissue responses to stress exposure. The third objective is to achieve research and educational integration through activities for high school students and undergraduate students incorporating tissue engineering, cardiovascular physiology, biomanufacturing, and stem cell biology. As part of the outreach efforts, a series of STEM based games will be developed and used as a centerpiece for community outreach in local, rural school districts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人体心脏是一个重要的器官，负责将血液泵送到身体的其他部位。这个泵能够加速或减速，以确保在活动或休息期间有足够的血液通过我们的身体。心脏能够通过神经系统的控制来实现泵送速率的这种变化。神经元向心脏发送信号以改变心跳速率，并帮助确保心脏跳动一致。这个教师早期职业发展（CAREER）项目支持基础研究，以了解神经元如何连接到心脏和改善心脏功能。这项研究将通过在三维工程结构中使用干细胞来研究神经元如何连接到心脏细胞以及神经元的电刺激如何改善跳动的心脏功能来实现。结果将有助于推进心脏生物学的知识，将促进潜在未来疗法的工程解决方案，并可用作药物筛选平台。该项目与纽约南部的社区外展活动完全结合。该研究员的长期职业目标是成为干细胞和组织工程领域的科学领导者，特别关注心血管组织模型和生物制造。为了实现这一目标，本CAREER项目的目标是询问自主神经刺激对体外工程心脏组织功能的作用。 详细了解心脏中发生的多细胞相互作用是提高工程心脏模型性能的必要但具有挑战性的方面。研究和教育计划分为三个不同的目标。第一个目标是设计异型多细胞模型来测量自主神经支配对心脏收缩行为和细胞组成的影响。为了实现这一目标，多能干细胞将分化为交感神经元和副交感神经元。将这些神经元细胞群与不同发育阶段的心肌细胞混合，以研究它们对心率、收缩力和钙处理动力学的影响。第二个目标是开发一种变频电刺激生物反应器，以模拟心肌细胞从自主神经元接收的信号。将在可变电刺激下培养心脏组织，并将其收缩特性直接与神经支配和非神经支配组织进行比较，以确定可变电刺激是否改善心脏组织对应力暴露的反应。第三个目标是通过高中生和本科生的活动，结合组织工程学，心血管生理学，生物制造和干细胞生物学，实现研究和教育的融合。作为推广工作的一部分，一系列基于STEM的游戏将被开发并用作当地农村学区社区推广的核心。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。