RECODE: Real-time analysis and environmental feedback for directed differentiation of liver organoids

人类干细胞可以培养成器官的模拟物，被称为“类器官”。如果它们能忠实地再现器官的关键结构和活动，它们将是非常有价值的。它们可能会彻底改变我们发现和测试新药、研究人类疾病的方式，甚至可能替换受损的身体部位。生产稳定可靠的有机化合物的技术还不存在。该项目将把一种新型的活体成像显微镜与自适应生物材料技术相结合，以实现对肝脏器官的主动监测和操纵。作为该项目的一部分，调查人员将在高中、本科生和研究生层面招募和培训不同的学生。他们还将向未得到充分服务的小学生推广科学活动，并从事高中教育工作者的发展。将人体干细胞三维(3D)培养为“有机物质”具有巨大的临床潜力。应用包括药物发现、安全性和有效性测试、再生医学，以及作为正常和疾病组织发育的模型。对于这些应用的成功，一个尚未满足的要求是适当的有机体分化和成熟。通过这一Recode项目，将开发一种非侵入性成像方法，以主动监测人类诱导多能干细胞(IPSCs)。这些信息将被用来操纵适应性生物材料。这些生物材料将调节基质介导的生物力学和生化线索，并可重复地指导有机物的分化。最后，将通过代表肝脏有机类化合物的三个主要潜在应用的分析来验证经编码分化的有机类化合物的改进的重复性和功能性：再生医学、药物筛选和疾病建模。开发的新技术将广泛适用于各种其他细胞、有机物和组织类型。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Human stem cells can be grown into organ mimics, termed “organoids”. If they can faithfully reproduce the key structures and activities of organs, they would be extremely valuable. They could revolutionize the way we discover and test new drugs, study human disease, and possibly even replace damaged body parts. The technology to produce consistent and reliable organoids does not exist. This project will combine a novel type of live imaging microscopy with adaptive biomaterials technology to enable active monitoring and manipulation of liver organoids. As part of the project, the investigators will recruit and train diverse students at the high school, undergraduate, and graduate levels. They will also promote science activities to under-served elementary students, and engage in high school educator development.Three-dimensional (3D) culture of human stem cells as “organoids” has tremendous clinical potential. Applications include drug discovery, safety and efficacy testing, regenerative medicine, and as models of normal and diseased tissue development. An unmet requirement for the success of these applications is proper organoid differentiation and maturation. Through this RECODE project, a noninvasive imaging method to actively monitor human induced pluripotent stem cells (iPSCs) will be developed. This information will be used to manipulate adaptive biomaterials. These biomaterials will modulate matrix-mediated biomechanical and biochemical cues and reproducibly direct organoid differentiation. Finally, the improved reproducibility and functionality of the RECODE-differentiated organoids will be validated through assays that represent the three major potential applications for hepatic organoids: regenerative medicine, drug screening, and disease modeling. The novel technologies developed will have broad applicability to a variety of other cell, organoid, and tissue types.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.