Back to search

BIOTEK2021-Bioteknologi for verdiskaping

DL: Emulating life in 3D with digital and experimental tissue models

Alternative title: Digitale og eksperimentelle vevsmodeller for etterligning av liv i 3D

Awarded: NOK 19.7 mill.

Cell cultures are important experimental tools in medical research. When cells are grown or cultured outside the body, they are grown in single layers on hard plastic. In the bodies of humans or animals, however, cells develop in far more complex soft three dimensional structures. Consequently, the cells that we grow in cultures outside of the body develop differently from cells in tissues and organs inside the body. This poses a problem: Studying tissue biology, disease progression, and the testing of different medicinal compounds using todays cell cultures does not provide sufficiently representative experimental models. 3DLife aims to develop novel strategies for making cell cultures that more closely mimic the conditions and environments that are found in the body. Instead of culturing cells in single layer cultures, we aim to generate new growth matrix materials and to employ these materials in advanced cell cultures with three-dimensional structures. High capacity methods for determining the cells gene expression, meaning how the cells respond to and behave in, their new three-dimensional environments, must be developed. Analysis of gene expression results in vast amounts of data. By using these data in computer models, we can identify key factors in making cell cultures that much more accurately resemble the normal cells, tissues and organs found in the body. These tailored cell cultures would serve as tissue and organ models for biomedical research and thus speeding up the development of novel therapeutic approaches. In the first part of the project, we have made new materials with controllable mechanical and biological properties, and adjusted materials and methods for the handling by robots for high-throughput screening. Detailed characterization of the gels includes novel studies by atomic force microscopy that reveals the surface structures and detailed mechanical mapping of the soft hydrogel structures. We have cultured different cell types in the gels and also adjusted materials and methods to be compatible with high cell viability. Fibroblasts, an important cell type for the development of tissue, respond differently to the different materials. The cells adhere to some materials when cultured on top. When the cells are inside the gels, the cell morphology is changing with the materials. We are now evaluating gene expression profiles from the fibroblasts to analyze how the cells are responding to the different hydrogels. We are now also investigating the gene expression profiles of fibroblasts from different parts of the body in our hydrogels. By comparing our data to existing datasets of primary human fibroblasts from different tissue, we aim to see if the materials influence cell phenotype. We currently further develop our hydrogel systems to include structures that is needed for the perfusion of culture medium through the tissue constructs. Both structures and fluid flow will influence the cell responses.The hydrogel structuring will form the basis of a perfused device and chip system for tissue-on-chip that will further mimic natural tissue.

Cell culture-based experiments are important pillars in all medically related research, allowing examination of living cells without the use of research animals or human subjects. However, the commonly used cellular monolayer cultures are a remote reflection of in vivo conditions, due to a lack of the cellular, structural and chemical elements forming the tissue microenvironment. This disparity results in cells losing their tissue-like phenotype over time, limiting the potential of the models for studying tissue biology and disease progression, and for testing pharmaceutic and toxic compounds. 3DLife aims to develop novel strategies for microtissue engineering in 3D, to provide model systems of organ function and bridge the gap to in vivo conditions. To understand how the microenvironment affects cells we will synthesize novel and tuneable extracellular scaffold materials, and develop tools for high-throughput screening (HTS) of 3D cell cultures to assess genetic expression patterns in response to defined scaffold properties. These advances have limited translational potential without a digital approach that can process the vast data output from HTS analyses and provide a systems-level understanding of material-cell interactions. By applying a computational model, we can predict the requirements of organotypic cells to their microenvironment and tailor materials for improved in vivo-like tissue and organ models for research and clinical applications beyond the state of the art. To achieve this ambitious goal, 3DLife brings in expert competence within material engineering, high-throughput analyses, transcriptomics and bioinformatics, cell biology and cultivation, microsystem technology and mathematical and computational modelling from NTNU and SINTEF supported by international academic collaboration. The project will contribute to the Centre for Digital Life Norway (DLN) with new knowledge, materials and methodology with a broad field of application in biotechnology.

Publications from Cristin

No publications found

No publications found

Funding scheme:

BIOTEK2021-Bioteknologi for verdiskaping