Microarchitectural mimicking of stroma-induced vasculature compression in pancreatic tumors using a 3D engineered model

作     者：Marcel Alexander Heinrich Irene Uboldi Praneeth Reddy Kuninty Marc J.K.Ankone Joop van Baarlen Yu Shrike Zhang Kartik Jain Jai Prakash 

作者机构：Department of Advanced Organ Bioengineering and TherapeuticsEngineered Therapeutics SectionTechnical Medical CentreUniversity of Twente7500AEEnschedethe Netherlands Laboratorium Pathologie Oost-Nederland(LabPON)7550 AMHengelothe Netherlands Division of Engineering in MedicineDepartment of MedicineBrigham and Women’s HospitalHarvard Medical School65 Landsdowne StCambridgeMA02139USA Department of Thermal and Fluid EngineeringBiofluid Dynamics SectionUniversity of Twente7500 AE Enschedethe Netherlands 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第22卷第4期

页      面：18-33页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0836[工学-生物工程] 

基　　金：Col/Fib PSCs Louisiana Department of Health, LDH Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO Stichting voor de Technische Wetenschappen, STW KWF Kankerbestrijding, DCS, (15204, STW/ KWF) 

主　　题：Pancreatic ductal adenocarcinoma Cancer-associated fibroblasts Collagen Fibrinogen Computational flow dynamics 3D in vitro model 

摘      要：Fibrotic tumors,such as pancreatic ductal adenocarcinoma(PDAC),are characterized for high desmoplastic reaction,which results in high intra-tumoral solid stress leading to the compression of blood *** microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of ***,there is a lack of relevant in vitro models capable of replicating these mechanical characteristics and to test anti-desmoplastic ***,a multi-layered vascularized 3D PDAC model consisting of primary human pancreatic stellate cells(PSCs)embedded in collagen/fibrinogen(Col/Fib),mimicking tumor tissue within adjunct healthy tissue,is presented to study the fibrosis-induced compression of vasculature in *** is demonstrated how the mechanical and biological stimulation induce PSC activation,extracellular matrix production and eventually vessel *** clinical relevance is confirmed by correlating with patient transcriptomic ***,the effects of gradual vessel compression on the fluid dynamics occurring within the channel is evaluated in ***,it is demonstrated how cancer-associated fibroblast(CAF)-modulatory therapeutics can inhibit the cell-mediated compression of blood vessels in PDAC in vitro,in silico and in *** is envisioned that this 3D model is used to improve the understanding of mechanical characteristics in tumors and for evaluating novel anti-desmoplastic therapeutics.