#lab model

Fusion Power

As one of your body's heaviest organs, your brain is packed with billions of neurons. No surprises there. But it also has a network of blood vessels that draws a staggering 20% of all the blood your heart pumps out. Mimicking this assembly of neurons and blood vessels in the lab is challenging. Current lab-grown models – brain organoids – lack blood vessel networks. Researchers now present a solution: fused organoids. Using human embryonic stem cells, brain organoids and blood vessel organoids were grown separately. They were then paired together, grown in 3D matrices and subsequently fused to each other. Fluorescence microscopy of the fused organoids (pictured), which contained neurons (white) and blood vessels (red), revealed structures similar to the blood-brain barrier and immune cells specific to the brain called microglia. These organoids, therefore, provide more accurate models of the brain that support research into the interactions between neurons and other brain cells.

Written by Lux Fatimathas

Image from work by Xin-Yao Sun and Xiang-Chun Ju, and colleagues

Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, and School of Life Science and Technology, ShanghaiTech University, Shanghai, China

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, May 2022

First Encounters

When you meet someone new do you react differently depending on whether you’re alone or surrounded by friends and family? Cells of the body respond to intruding microbes in concert with their neighbours, but many experiments into how the gut interacts with external factors are based on single layers of particular cells in a dish. A new approach cultured a 3D model, pictured after exposure to bacteria, complete with intestinal lining (stained green and red) and immune cells (purple), allowing a more representative overview of interactions. With the culture established, the researchers tested the platform’s use, introducing elements such as parasitic worm excretions to observe the resulting physical and functional changes in the intestinal lining. They saw lifelike changes in the regulation of immune system proteins, confirming the model’s viability, and showcasing its potential to eavesdrop on the interactions between host and microbe.

Written by Anthony Lewis

Image from work by Chrysanthi-Maria Moysidou and colleagues

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Advanced Materials, June 2022

Partners in Crime

Gonorrhoea, chlamydia, genital herpes, human papillomavirus (HPV) – all of these infections target the womb entrance, the cervix. A lack of cervical models makes studying these infections difficult. Researchers now present cervical organoids, made from human ectocervical [vaginal end of the cervix] cells, to investigate infection with a cancer-causing strain of HPV alone or in combination with chlamydia. Half of the organoids were genetically manipulated to introduce HPV genes into their DNA, mimicking what happens during HPV infection. Fluorescence microscopy revealed HPV organoids (pictured, right) matured similarly to non-HPV organoids (left) but with signs of precancerous lesions. When infected with chlamydia both types of organoid showed changes in gene activity relating to the cells' immune responses. Notably, chlamydia co-infection suppressed genetic changes that HPV is known to cause that promote DNA repair. The organoid model, therefore, highlights how coinfections change how the cervix responds, potentially affecting cancer progression in HPV infections.

Written by Lux Fatimathas

Image adapted from work by Stefanie Koster and Rajendra Kumar Gurumurthy, and colleagues

Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, February 2022

Intestines ‘n’ Chips

In children, the triple threat of poor sanitation, gut infections and malnutrition can cause environmental enteric dysfunction (EED). This inflammatory condition damages the gut lining, disturbing its ability to act as a barrier and absorb nutrients, as well as eroding its special projections called villi. Researchers now present a way to model this disease in the lab using organ chips. Organ chips mimic the function of whole organs. Here, chips were made using intestinal cells from healthy or EED patients. Exposing EED chips to conditions mimicking malnutrition caused changes in gene activity matching those in intestinal samples from EED patients. Fluorescence microscopy revealed extended villi (left) in both healthy (top) and EED (bottom) chips. In both chips, the absence of nutrients caused villi to erode (right), and impaired barrier function and nutrient uptake. However, EED chips additionally released inflammatory chemicals. Intestine chips can, therefore, accurately model EED for future studies.

Written by Lux Fatimathas

Image from work by Amir Bein and Cicely W. Fadel, and colleagues

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Biomedical Engineering, June 2022

Model Behaviour

Even in the earliest stages of pregnancy problems can occur. As the newly formed embryo attaches to the lining of the womb, called the endometrium, the lining changes to prepare for pregnancy. During this transformation some cells stop dividing in a process called senescence. When this happens in excess it can lead to recurrent miscarriages, and when senescence is lacking embryos can fail to implant properly. To further our knowledge of these early moments of pregnancy, researchers have developed a new model of the human endometrium which, when hormones are added, mimics the implantation environment. Using a drug called dasatinib to eliminate senescent cells, the team captured a time-lapse of a replica implantation failure, where cell movement towards the embryo stopped, and the embryo failed to expand. In the future this model could be used to test potential treatments for pregnancy disorders.

Written by Katy Pallister

Video from work by Thomas M Rawlings and colleagues

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, September 2021

Super Models

Transmitted by ticks, flaviviruses like Kyasanur Forest disease virus (KFBV) and its close relative Alkhurma haemorrhagic fever virus (AHFV) are emerging threats for global health. With a small but growing number of cases, and an expanding range in India and the Middle East respectively, these viruses can cause fatal haemorrhagic fevers, but remain relatively-poorly understood. Typical laboratory animals like mice can be infected with both viruses, but the diseases often manifest very differently compared to human patients. Among primates, rhesus macaques (Macaca mulatta), are largely protected by a protein hindering viral replication, but pigtailed-macaques (Macaca nemestrina) are not. Infecting them with KFBV or AHFV triggers symptoms more consistent with those of humans, with virus particles found in the gut and lymph system (pictured are KFBV particles, in red, in a lymph node). As a model system, this species could help us better understand these viruses, and potentially develop future vaccines.

Written by Emmanuelle Briolat

Image from work by Rebecca M. Broeckel and colleagues

Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Research published in PLOS Pathogens, December 2021

Mammary Makers

While mammary ducts are essential to developing breast tissue and milk production, they are also prone to genetic mutations which may lead to cancer. To investigate, scientists grew these 'model' ducts (highlighted in turquoise) from human mammary cells in the lab, while also recreating their microenvironment of nearby blood vessels (in green with blue nuclei). The middle and right ducts developed from healthy cells mixed with cells harbouring mutations in important genes – with drastic effects on their development and shape compared to the healthy duct (left). Surprisingly, chemicals produced by the mutated ducts affect cells in nearby vessels, leaving them weakened and 'leaky'. Such biology-mimicking models continue to offer perspectives on cancer that may be difficult to investigate in living tissues, and future studies may suggest how chemical messages between these tissues, an example of paracrine signalling, may be switched on or off during development or disease.

Written by John Ankers

Image adapted from work by Matthew L. Kutys and William J. Polacheck, and colleagues

Department of Biomedical Engineering, Boston University, Boston, MA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, July 2020