• search hit 6 of 6
Back to Result List

Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing

Please always quote using this URN: urn:nbn:de:bvb:20-opus-231465
  • High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrixHigh attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Johanna Kühnemundt, Heidi Leifeld, Florian Scherg, Matthias Schmitt, Lena C. Nelke, Tina Schmitt, Florentin Bauer, Claudia Göttlich, Maximilian Fuchs, Meik Kunz, Matthias Peindl, Caroline Brähler, Corinna Kronenthaler, Jörg Wischhusen, Martina Prelog, Heike Walles, Thomas Dandekar, Gudrun Dandekar, Sarah L. Nietzer
URN:urn:nbn:de:bvb:20-opus-231465
Document Type:Journal article
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Medizinische Fakultät / Kinderklinik und Poliklinik
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):ALTEX
Year of Completion:2021
Volume:38
Article Number:2
Pagenumber:289-306
Source:ALTEX 38(2), 289-306. doi:10.14573/altex.2008141
DOI:https://doi.org/10.14573/altex.2008141
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:bioreactor culture; combinatorial drug predictions; immunotherapies; invasiveness; modular tumor tissue models
Release Date:2021/04/22
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2020
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International