Biomimetic hydrogels with mesoscale collagen architecture for patient-derived tumor organoids culture  

作　　者：Jiaxin Wang Zhilin Sui Wei Huang Zhentao Yu Ling Guo 

机构地区：[1]Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academic of Medical Sciences&Peking Union Medical College,Shenzhen,518116,China [2]Center for Cell and Gene Circuit Design,CAS Key Laboratory of Quantitative Engineering Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,Guangdong,China [3]Department of Biology,Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,China

出　　处：《Bioactive Materials》2024年第8期384-398,共15页生物活性材料（英文）

基　　金：supported by the National Key R&D Program of China(2019YFA0906000);National Natural Science Foundation of China 82273308;this work was supported by the Shenzhen Science and Technology Program(JCYJ20220530112817040,ZDSYS20220606101604009,JHZ20220913142804008);Sanming Project of Medicine in Shenzhen(SZSM201612097);Shenzhen Key Medical Discipline Construction Fund(No.SZXK075);Shenzhen Medical Research Fund(D2301001);Shenzhen High-level Hospital Construction Fund;Sponsored by National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen E010122002.

摘　　要：Patient-derived tumor organoids(PDTOs)shows great potential as a preclinical model.However,the current methods for establishing PDTOs primarily focus on modulating local properties,such as sub-micrometer topographies.Nevertheless,they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression.In this study,we present a rapid technique for generating collagen bundles with an average length of 90±27μm and a mean diameter of 5±1.5μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion.The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels,incorporating microbial transglutaminase(mTG)crosslinked gelatin.These biomimetic hydrogels,referred to as MC-gel,were specifically designed for patient-derived tumor organoids.The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle;moreover,their irregular morphology more closely resembled that observed in vivo.The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue.Additionally,these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices.This recently developed model holds great potential for investigating the occurrence,progression,metastasis,and management of tumors,thereby offering opportunities for personalized medicine and customized treatment options.

关 键 词：Extracellular matrix(ECM) Mesoscale architecture Collagen bundles Lung cancer organoids(LCOs) Biomimetic hydrogel 

分 类 号：R318[医药卫生—生物医学工程] TQ427.26[医药卫生—基础医学]