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

RECODE：实时分析和环境反馈，用于肝脏类器官的定向分化

• 批准号: 2033302
• 负责人: Sarah Heilshorn
• 金额: $ 142.59万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2033302&HistoricalAwards=false
• 关键词: RECODE; Real; time; analysis; environmental

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.

人类干细胞可以生长成器官模拟物，称为“类器官”。如果它们能够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。 它们可以彻底改变我们发现和测试新药的方式，研究人类疾病，甚至可能替换受损的身体部位。生产一致和可靠的类器官的技术并不存在。该项目将联合收割机与自适应生物材料技术相结合，以实现对肝脏类器官的主动监测和操作。作为该项目的一部分，调查人员将招募和培训高中、本科和研究生阶段的不同学生。他们还将向服务不足的小学生推广科学活动，并参与高中教育工作者的发展。三维（3D）培养人类干细胞作为“类器官”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，以及作为正常和患病组织发育的模型。这些应用成功的未满足的要求是适当的类器官分化和成熟。通过该RECODE项目，将开发一种非侵入性成像方法来主动监测人类诱导多能干细胞（iPSC）。 这些信息将用于操纵自适应生物材料。这些生物材料将调节基质介导的生物力学和生物化学线索，并可重复地指导类器官分化。最后，RECODE分化的类器官的改进的再现性和功能性将通过代表肝类器官的三个主要潜在应用的测定进行验证：再生医学，药物筛选和疾病建模。该奖项反映了NSF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。

项目成果

Transient Competitors to Modulate Dynamic Covalent Cross-Linking of Recombinant Hydrogels

调节重组水凝胶动态共价交联的瞬时竞争剂

• DOI: 10.1021/acs.chemmater.3c01575
• 发表时间: 2023
• 期刊: Chemistry of Materials
• 影响因子: 8.6
• 作者: Gilchrist, Aidan E.;Liu, Yueming;Klett, Katarina;Liu, Yu-Chung;Ceva, Sofía;Heilshorn, Sarah C.
• 通讯作者: Heilshorn, Sarah C.

Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology.

• DOI: 10.1002/adhm.202200011
• 发表时间: 2022-07
• 期刊: ADVANCED HEALTHCARE MATERIALS
• 影响因子: 10
• 作者: Navarro, Renato S.;Huang, Michelle S.;Roth, Julien G.;Hubka, Kelsea M.;Long, Chris M.;Enejder, Annika;Heilshorn, Sarah C.
• 通讯作者: Heilshorn, Sarah C.

A human multi-lineage hepatic organoid model for liver fibrosis.

• DOI: 10.1038/s41467-021-26410-9
• 发表时间: 2021-10-22
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Guan Y;Enejder A;Wang M;Fang Z;Cui L;Chen SY;Wang J;Tan Y;Wu M;Chen X;Johansson PK;Osman I;Kunimoto K;Russo P;Heilshorn SC;Peltz G
• 通讯作者: Peltz G

3D printing microporous scaffolds from modular bioinks containing sacrificial, cell-encapsulating microgels.

使用含有牺牲性细胞封装微凝胶的模块化生物墨水 3D 打印微孔支架。

• DOI: 10.1039/d3bm00721a
• 发表时间: 2023
• 期刊: Biomaterials science
• 影响因子: 6.6
• 作者: Seymour,AlexisJ;Kilian,David;Navarro,RenatoS;Hull,SarahM;Heilshorn,SarahC
• 通讯作者: Heilshorn,SarahC

Cell Microencapsulation Within Engineered Hyaluronan Elastin-Like Protein (HELP) Hydrogels.

工程透明质酸弹性蛋白样蛋白 (HELP) 水凝胶内的细胞微囊化。

• DOI: 10.1002/cpz1.917
• 发表时间: 2023
• 期刊: Current protocols
• 作者: Hefferon,MeghanE;Huang,MichelleS;Liu,Yueming;Navarro,RenatoS;dePaivaNarciso,Narelli;Zhang,Daiyao;Aviles-Rodriguez,Giselle;Heilshorn,SarahC
• 通讯作者: Heilshorn,SarahC