PFI (MCA): Modeling the Transport of Pharmaceutical Agents Across the Placental Barrier

这个创新伙伴关系-中期职业发展（PFI-MCA）项目的更广泛的影响/商业潜力在于创新的方法和平台技术-集成了3D细胞培养，传感和成像。该系统将进一步了解生理过程，并可以使用每个准妈妈的干细胞为其个性化，从而提高特定化合物运输率测试的准确性，并设置安全暴露水平。该项目的成功完成将产生一种经济且与生理相关的工具，可用于测试更多的化合物，促进高通量筛选和快速数据收集，从而确保该技术的市场潜力。拟议的项目提出了一种范式转变，从目前用于研究药物通过胎盘屏障的运输及其对发育中的胎盘的影响的方法。该平台将复制生理基质力学、血流动力学和化合物通过胎盘屏障的能力，这将使定量研究能够在广泛的药物上进行，以了解它们的相互作用，包括通过脉管系统的运输，以及通过胎盘屏障的易位扩散到胎儿血流中。此外，该系统最终可以利用每位准妈妈的干细胞进行个性化设计。这可以提高测试某些化合物传输速率的准确性，同时降低成本，实现实时监测和快速数据收集。总的来说，所提出的技术能够理解胎盘中的关键代谢和炎症过程，为其未来潜在的商业化奠定基础。该项目由创新伙伴计划和促进竞争研究的既定计划（EPSCoR）共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Partnerships for Innovation – Mid Career Advancement (PFI-MCA) project lies in an innovative approach and platform technology – integrating 3D cell culture, sensing, and imaging. This system will further enable understanding of physiological processes and can be personalized for each expecting mother using their stem cells, leading to higher accuracy in testing for the transport rate of specific compounds and setting safe exposure levels. The successful completion of this project will lead to an economical and physiologically relevant tool that accommodates testing of a larger number of compounds, facilitates high-throughput screening and rapid data collection, and thus ensures market potential for this technology.The proposed project presents a paradigm shift from the approach currently used to study the transport of pharmaceutical drugs through the placental barrier and their effects on the developing placenta. This platform will replicate the physiological matrix mechanics, hemodynamics, and compound’s ability to permeate through the placental barrier, which will enable quantitative studies to be performed on a vast range of pharmaceuticals to understand their interactions, including transport through the vasculature, and translocation across the placental barrier to diffuse into the fetal blood stream. Furthermore, the system can ultimately be personalized for each expecting mother using their stem cells. This could lead to higher accuracy in testing the transport rate of certain compounds while reducing the cost and enabling real-time monitoring and rapid data collection. Collectively, the proposed technology enables the understanding of critical metabolic and inflammatory processes in the placenta, laying the foundation for its potential commercialization in the future.This project is jointly funded by the Partnerships for Innovation program and the Established Program to Stimulate Competitive Research (EPSCoR).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.