Building Mini Lungs on Microchips to Revolutionize Infection Study and Drug Development
The COVID-19 pandemic highlighted the need for in-depth and efficient study of infectious diseases. Understanding the mechanisms behind how a virus infiltrates the human body is a complex process that requires the control of various variables. Researchers from Rockefeller University collaborated to refine a cell culture technology platform that produces genetically identical lung buds, the embryonic structures that give rise to respiratory organs, from human embryonic stem cells (hESCs). They then placed these buds on a microchip that allowed them to study thousands of infections at once, leading to unprecedented high-throughput analysis of lung tissue infection without the nosy variables. The technology hinges on the ability of genetically identical tissues from the first moment of infection to illuminate the pathogen’s path, shedding light on which cells get infected and when, the level of infection, and how it differs under different conditions.
The Possibility of Tracking Thousands of Infections at Once
The technology could revolutionize the understanding of infections and the development of drugs and treatments to combat them. It provides unlimited, fast, and scalable access to lung tissue that has the key features of human lung development and can be used to track lung infections and identify candidate therapies. These lungs are clones that have the same DNA signature, so researchers no longer have to worry about one patient responding differently from another. Quantification allows them to keep the genetic information constant and measure the key variable – the virus.
Embryonic Stem Cells and Infinite Possibilities
The Embryonic stem cells are the Ur cells of the human body. They can divide infinitely to create more stem cells or to differentiate into any other tissue. This potential has been long explored by Brivanlou’s Synthetic Biology Laboratory. The team used a microchip array and stimuli from four main signaling pathways that induce stem cells to differentiate into specific cell types. The lung cells took about two weeks to form identical buds whose molecular profiles closely matched those seen in early fetal lung development. The buds had the full tissue complexity that consisted of the formation of airways and alveoli structures known to be damaged in many cases of people with severe COVID.
Identifying the Vulnerability of Alveoli
The platform was used to study how SARS-Co-V2 infects different lung cells. The alveoli are small sacs at the end of the pulmonary branches that manage the gas exchange that takes place with each breath. Researchers found that these sacs were more susceptible to SARS-Co-V-2 infection than airway cells, which are the organ’s gatekeepers – the first defense against every inhaled threat. The alveoli’s vulnerability was blamed on the BMP signaling pathway, which made the cells more vulnerable to infection. Blocking the BMP pathway made the cells less vulnerable.
Beyond COVID and Its Limitations
The technology presents an opportunity to investigate the mechanisms of influenza, RSV, lung diseases, and lung cancer, among other diseases. It can also detect new drugs used to develop treatment methods. The lungs aren’t the only target organ, and the researchers plan to focus on the liver, kidneys, and pancreas in upcoming studies. The technology could also be used to respond to future pandemics with much more speed and precision. It offers a way to make a virus visible and develop therapeutics faster than what was possible during COVID. It can also be used to detect drugs, vaccines, compounds, monoclonal antibodies, and more directly in human tissue.
Limitations Around the Technology
Not everyone is convinced that the synthetic lungs being used to study COVID are an accurate representation of the organs in the human body. However, beyond the limitations, the study’s findings offer insights into how diseases spread rapidly and target different human organs. The technology could herald the future of rapid drug development and help scientists respond to the most dangerous diseases that affect humanity.
Emerging Technology Can Revolutionize Drug Development and Data Analysis
The use of microchips as tools for medical research is ubiquitous. Researchers have been testing their abilities in lung cancer studies, drug development, and drug discovery, and the possibilities are endless. They offer speed, accuracy, and large amounts of data that could be used in drug discovery and development, making them useful to pharmaceutical companies. Microchips open the world of possibilities in drug development, from testing toxicity, efficacy, intercellular signaling, to research on the most complex diseases.
Additionally, it holds immense potential for the expansion of personalized medicine, creating patient-specific developing drugs, and personalized treatment options. In doing so, it can reduce the cost of developing drugs and increase the cost-effectiveness of drug discovery.
Conclusion
The technology used to create genetically identical lung buds from embryonic cells, and then using them to understand lung infections and candidate therapies is a game-changer. It presents an opportunity to investigate the pathogenesis of various infections, including COVID-19, and identify potential drug treatments and therapies. The high-throughput analysis of lung tissue infections allowed for easy tracking of thousands of infections at once, shedding light on cells that get infected and when, the level of infection, and how it differs. The technology’s future looks promising, with more research ongoing into its potential and limitations.
—————————————————-
| Article | Link |
|---|---|
| UK Artful Impressions | Premiere Etsy Store |
| Sponsored Content | View |
| 90’s Rock Band Review | View |
| Ted Lasso’s MacBook Guide | View |
| Nature’s Secret to More Energy | View |
| Ancient Recipe for Weight Loss | View |
| MacBook Air i3 vs i5 | View |
| You Need a VPN in 2023 – Liberty Shield | View |
When we’re driving to a new destination, we often turn down the volume on the stereo as we follow directions. What had been music suddenly sounds like noise and interferes with our focus.
Our understanding of how infectious diseases like COVID affect human lungs has been similarly confounded by noise. Data from patients’ lung tissues varies greatly from person to person, obscuring the basic mechanisms of how, exactly, SARS-Co-V2 first infects lung cells. It’s also an after-the-fact analysis, as if we were trying to map the route the virus took three states ago.
Rejecting the noise of variability by studying genetically identical tissues from the very first moment of infection could illuminate the path the pathogen takes. What cells get infected and when? What is the level of infection and how does it differ by cell type? How does it change under different conditions?
What if it were possible to track thousands of these infections at once? It could revolutionize our understanding of both infections and the drug treatments used to combat them.
That’s the hope for a new advanced technology capable of growing mini organs on microchips. The labs of Rockefeller’s Ali Brivanlou and Charles M. Rice collaborated to refine a cell culture technology platform that produces genetically identical lung buds, the embryonic structures that give rise to our respiratory organs, from human embryonic stem cells (hESCs). . Their findings were recently published in Stem Cell Reports.
When placed on a microchip array and carefully dosed with a custom cocktail of signaling molecules, hESCs rapidly organize into “microlungs” that have full tissue complexity. These sprouts can be cultured by the thousands, allowing for unprecedented high-throughput analysis of lung tissue infection without all the noisy variables.
The result is unlimited, fast, and scalable access to lung tissue that has the key features of human lung development and can be used to track lung infections and identify candidate therapies.
“These lungs are basically clones,” says Ali Brivanlou. “They have the exact same DNA signature. That way, we don’t have to worry about one patient responding differently from another. Quantification allows us to keep the genetic information constant and measure the key variable: the virus.”
Building a better mini lung
Embryonic stem cells are the Ur cells of the human body. They can divide infinitely to create more stem cells or to differentiate into any other tissue. The Brivanlou Synthetic Biology Laboratory has long explored its potential.
Brivanlou joined forces with Rockefeller colleague Charles M. Rice during the COVID pandemic: his lab had the microchip technology to grow lung buds, and Rice’s lab had the necessary biosafety clearance to infect them with SARS-Co- V2 and study the result.
In 2021, first authors Edwin Rosado-Olivieri, a stem cell biologist in Brivanlou’s lab, and Brandon Razooky, then a postdoc in Rice’s Laboratory of Virology and Infectious Diseases, began to persuade cells to organize themselves into more specialized forms. Stem cells do not organize themselves. They need a confined space, like a microchip pit, and stimuli to bring about change. The stimuli come from four main signaling pathways that induce stem cells to differentiate into specific cell types.
After about two weeks, the group’s lung cells had formed identical buds whose molecular profiles closely matched those seen in early fetal lung development, including the formation of airways and alveoli, structures known to be damaged in many cases. people with severe COVID.
Identify a key culprit
Since then, they have used the platform to understand how SARS-Co-V2 infects different lung cells.
The alveoli are small sacs at the end of the pulmonary branches that manage the gas exchange that takes place with each breath: oxygen in, carbon dioxide out. By studying cells from the mass-cloned alveoli, the researchers found that the alveoli were more susceptible to SARS-Co-V-2 infection than airway cells, which are the organ’s gatekeepers, the first defense against all inhaled threats. If the virus got through, the alveoli were easy prey.
Another view of virus particles (blue) infecting alveolar and respiratory tract tissues (red).
They also found a winning combination of signaling proteins to create the most robust batches of lung buds: a mix of keratinocyte growth factor (KGF) and bone morphogenetic protein 4 (BMP4). Both contribute to cell differentiation and growth.
Interestingly, the BMP pathway has a drawback. When they compared infected lung buds with postmortem tissue from COVID patients, they found that the BMP signaling pathway was induced in both, making the tissues more vulnerable to infection. Blocking the BMP pathway made the cells less vulnerable.
Beyond COVID
The researchers note that the platform can also be used to investigate the mechanisms of influenza, RSV, lung diseases, and lung cancer, among other diseases. Also, it can be used to detect new drugs to treat them.
And the lungs are far from the only organ of interest. “The broader focus of our work is to understand cell development to create synthetic organs and tissues that we can use to model disease and find therapeutic mechanisms,” says Rosado-Olivieri. The liver, kidneys, and pancreas are likely the next targets.
“The platform will also allow us to respond to the next pandemic with much more speed and precision,” adds Brivanlou. “We can quickly capitalize on this platform to make a virus visible and develop therapeutics much faster than we did for COVID. It can be used to detect drugs, compounds, vaccines, monoclonal antibodies, and more directly in human tissue. This technology is ready-to-use.” to face all kinds of threats that may hit us in the future.”
https://www.sciencedaily.com/releases/2023/06/230601155927.htm
—————————————————-