Tag Archives: 3D scaffold

Better technique for growing organoids taking them from the lab to the clinic

A Nov. 16, 2016 École Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert) describes a new material for growing organoids,

Organoids are miniature organs that can be grown in the lab from a person’s stem cells. They can be used to model diseases, and in the future could be used to test drugs or even replace damaged tissue in patients. But currently organoids are very difficult to grow in a standardized and controlled way, which is key to designing and using them. EPFL scientists have now solved the problem by developing a patent-pending “hydrogel” that provides a fully controllable and tunable way to grow organoids. …

Organoids need a 3D scaffold

Growing organoids begins with stem cells — immature cells that can grow into any cell type of the human body and that play key roles in tissue function and regeneration. To form an organoid, the stem cells are grown inside three-dimensional gels that contain a mix of biomolecules that promote stem cell renewal and differentiation.

The role of these gels is to mimic the natural environment of the stem cells, which provides them with a protein- and sugar-rich scaffold called the “extracellular matrix”, upon which the stem cells build specific body tissues. The stem cells stick to the extracellular matrix gel, and then “self-organize” into miniature organs like retinas, kidneys, or the gut. These tiny organs retain key aspects of their real-life biology, and can be used to study diseases or test drugs before moving on to human trials.

But the current gels used for organoid growth are derived from mice, and have problems. First, it is impossible to control their makeup from batch to batch, which can cause stem cells to behave inconsistently. Second, their biochemical complexity makes them very difficult to fine-tune for studying the effect of different parameters (e.g. biological molecules, mechanical properties, etc.) on the growth of organoids. Finally, the gels can carry pathogens or immunogens, which means that they are not suitable for growing organoids to be used in the clinic.

A hydrogel solution

The lab of Matthias Lütolf at EPFL’s Institute of Bioengineering has developed a synthetic “hydrogel” that eschews the limitations of conventional, naturally derived gels. The patent-pending gel is made of water and polyethylene glycol, a substance used widely today in various forms, from skin creams and toothpastes to industrial applications and, as in this case, bioengineering.

Nikolce Gjorevski, the first author of the study, and his colleagues used the hydrogel to grow stem cells of the gut into a miniature intestine. The functional hydrogel was not only a goal in and of itself, but also a means to identify the factors that influence the stem cells’ ability to expand and form organoids. By carefully tweaking the hydrogel’s properties, they discovered that separate stages of the organoid formation process require different mechanical environments and biological components.

One such factor is a protein called fibronectin, which helps the stem cells attach to the hydrogel. Lütolf’s lab found that this attachment itself is immensely important for growing organoids, as it triggers a whole host of signals to the stem cell that tell it to grow and build an intestine-like structure. The researchers also discovered an essential role for the mechanical properties, i.e. the physical stiffness, of the gel in regulating intestinal stem cell behavior, shedding light on how cells are able to sense, process and respond to physical stimuli. This insight is particularly valuable – while the influence of biochemical signals on stem cells is well-understood, the effect of physical factors has been more mysterious.

Because the hydrogel is man-made, it is easy to control its chemical composition and key properties, and ensure consistency from batch to batch. And because it is artificial, it does not carry any risk of infection or triggering immune responses. As such, it provides a means of moving organoids from basic research to actual pharmaceutical and clinical applications in the future.

Lütolf’s lab is now researching other types of stem cells in order to extend the capacities of their hydrogel into other tissues.

Here’s a link to and a citation for the paper,

Designer matrices for intestinal stem cell and organoid culture by Nikolce Gjorevski, Norman Sachs, Andrea Manfrin, Sonja Giger, Maiia E. Bragina, Paloma Ordóñez-Morán, Hans Clevers, & Matthias P. Lutolf.  Nature (2016) doi:10.1038/nature20168 Published online 16 November 2016

This paper is behind a paywall.

Replicating brain’s neural networks with 3D nanoprinting

An announcement about European Union funding for a project to reproduce neural networks by 3D nanoprinting can be found in a June 10, 2016 news item on Nanowerk,

The MESO-BRAIN consortium has received a prestigious award of €3.3million in funding from the European Commission as part of its Future and Emerging Technology (FET) scheme. The project aims to develop three-dimensional (3D) human neural networks with specific biological architecture, and the inherent ability to interrogate the network’s brain-like activity both electrophysiologically and optically. It is expected that the MESO-BRAIN will facilitate a better understanding of human disease progression, neuronal growth and enable the development of large-scale human cell-based assays to test the modulatory effects of pharmacological and toxicological compounds on neural network activity. The use of more physiologically relevant human models will increase drug screening efficiency and reduce the need for animal testing.

A June 9, 2016 Institute of Photonic Sciences (ICFO) press release (also on EurekAlert), which originated the news item, provides more detail,

About the MESO-BRAIN project

The MESO-BRAIN project’s cornerstone will use human induced pluripotent stem cells (iPSCs) that have been differentiated into neurons upon a defined and reproducible 3D scaffold to support the development of human neural networks that emulate brain activity. The structure will be based on a brain cortical module and will be unique in that it will be designed and produced using nanoscale 3D-laser-printed structures incorporating nano-electrodes to enable downstream electrophysiological analysis of neural network function. Optical analysis will be conducted using cutting-edge light sheet-based, fast volumetric imaging technology to enable cellular resolution throughout the 3D network. The MESO-BRAIN project will allow for a comprehensive and detailed investigation of neural network development in health and disease.

Prof Edik Rafailov, Head of the MESO-BRAIN project (Aston University) said: “What we’re proposing to achieve with this project has, until recently, been the stuff of science fiction. Being able to extract and replicate neural networks from the brain through 3D nanoprinting promises to change this. The MESO-BRAIN project has the potential to revolutionise the way we are able to understand the onset and development of disease and discover treatments for those with dementia or brain injuries. We cannot wait to get started!”

The MESO-BRAIN project will launch in September 2016 and research will be conducted over three years.

About the MESO-BRAIN consortium

Each of the consortium partners have been chosen for the highly specific skills & knowledge that they bring to this project. These include technologies and expertise in stem cells, photonics, physics, 3D nanoprinting, electrophysiology, molecular biology, imaging and commercialisation.

Aston University (UK) Aston Institute of Photonic Technologies (School of Engineering and Applied Science) is one of the largest photonic groups in UK and an internationally recognised research centre in the fields of lasers, fibre-optics, high-speed optical communications, nonlinear and biomedical photonics. The Cell & Tissue Biomedical Research Group (Aston Research Centre for Healthy Ageing) combines collective expertise in genetic manipulation, tissue engineering and neuronal modelling with the electrophysiological and optical analysis of human iPSC-derived neural networks. Axol Bioscience Ltd. (UK) was founded to fulfil the unmet demand for high quality, clinically relevant human iPSC-derived cells for use in biomedical research and drug discovery. The Laser Zentrum Hannover (Germany) is a leading research organisation in the fields of laser development, material processing, laser medicine, and laser-based nanotechnologies. The Neurophysics Group (Physics Department) at University of Barcelona (Spain) are experts in combing experiments with theoretical and computational modelling to infer functional connectivity in neuronal circuits. The Institute of Photonic Sciences (ICFO) (Spain) is a world-leading research centre in photonics with expertise in several microscopy techniques including light sheet imaging. KITE Innovation (UK) helps to bridge the gap between the academic and business sectors in supporting collaboration, enterprise, and knowledge-based business development.

For anyone curious about the FET funding scheme, there’s this from the press release,

Horizon 2020 aims to ensure Europe produces world-class science by removing barriers to innovation through funding programmes such as the FET. The FET (Open) funds forward-looking collaborations between advanced multidisciplinary science and cutting-edge engineering for radically new future technologies. The published success rate is below 1.4%, making it amongst the toughest in the Horizon 2020 suite of funding schemes. The MESO-BRAIN proposal scored a perfect 5/5.

You can find out more about the MESO-BRAIN project on its ICFO webpage.

They don’t say anything about it but I can’t help wondering if the scientists aren’t also considering the possibility of creating an artificial brain.