Scientific experts have innovated a pioneering approach that harnesses microchip technology to generate miniature copies of human lungs from human embryonic stem cells (hESCs), providing a unique strategy for the investigation of lung infections such as COVID-19. This technique facilitates the self-organization of stem cells into intricate “micro lungs” that resemble the complexity of human lung tissue. It enables an unparalleled high-throughput analysis of lung tissue infection while reducing the inconsistency of using different patient samples. Moreover, this platform can be applied to examine other diseases, test potential drugs, and be prepared to respond rapidly to future pandemics. (Artist’s concept of lab-grown mini lungs.)
By leveraging a cell culture technology, scientists have devised a method to produce miniature copies of human lungs on microchips from stem cells. This innovative approach has provided insights into the vulnerability of alveoli cells to SARS-CoV-2 and demonstrated that mitigating a certain signaling pathway reduces susceptibility to infection. This platform also shows promise in the exploration of other diseases, drug screenings, and in preparing for future pandemics swiftly.
Analogous to turning down the stereo in the car when following directions to a new destination, scientists have had to tune out the noise in data to focus on understanding how infectious diseases like COVID impact the lungs. Data obtained from lung tissues of various patients introduce a significant amount of variability, obscuring the basic mechanisms of how SARS-CoV-2 initially infects lung cells.
By examining genetically identical tissues from the onset of infection, scientists could illuminate the path taken by the pathogen, the infected cells, the infection levels, how it varies across different cell types, and how it changes under various conditions. The potential to track thousands of these infections simultaneously could revolutionize our comprehension of infections and the drug treatments utilized to combat them.
This is the aspiration behind the development of new advanced technology that grows mini-organs on microchips. Researchers from Rockefeller’s Ali Brivanlou and Charles M. Rice’s labs collaborated to enhance a cell culture technology platform capable of growing identical lung buds—the embryonic structures leading to our respiratory organs—from human embryonic stem cells (hESCs). Their findings were recently published in the Stem Cell Reports journal.
When positioned on a microchip array and treated with a specialized concoction of signaling molecules, the hESCs quickly organize into “micro lungs” with complete tissue complexity. These buds can be cultured in their thousands, enabling an unparalleled high-throughput analysis of lung tissue infection without the usual inconsistencies. The outcome is swift, scalable, and unlimited access to lung tissue exhibiting the primary characteristics of human lung development that can be utilized to track lung infections and identify potential treatments.
The researchers’ collaborative work led to the development of miniature lungs, essentially clones, sharing the same DNA signature. This removed the usual variability seen in patient responses, focusing on the key variable – the virus.
The team combined their expertise during the COVID pandemic, leveraging microchip technology and the necessary biosafety clearance to study the effect of infecting these lung buds with SARS-CoV-2.
Within two weeks, the researchers were able to differentiate the stem cells into identical buds with molecular profiles closely resembling those seen in the earliest stages of fetal lung development. They have used this platform to gain insights into how SARS-CoV-2 infects different lung cells and identified a key signaling pathway contributing to increased vulnerability to infection.
This breakthrough platform has wider applications beyond COVID-19, potentially aiding in the study of influenza, RSV, pulmonary diseases, and lung cancer, among other diseases, and even serving as a tool to screen for new drugs.
The ultimate goal is to understand cellular development to create synthetic organs and tissues for disease modelling and identifying therapeutic mechanisms. The liver, kidney, and pancreas are likely the next targets. This technology is primed to respond to future pandemics with greater speed and precision, potentially enabling us to develop therapies faster than for COVID-19, and can be used to screen for drugs, compounds, vaccines, and monoclonal antibodies directly in human tissue.
Reference: “Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells” by E.A. Rosado-Olivieri, B. Razooky, J. Le Pen, R. De Santis, D. Barrows, Z. Sabry, H.-H. Hoffmann, J. Park, T.S. Carroll, J.T. Poirier, C.M. Rice and A.H. Brivanlou, 20 April 2023, Stem Cell Reports. DOI: 10.1016/j.stemcr.2023.03.015
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Frequently Asked Questions (FAQs) about Lab-Grown Miniature Lungs
How are researchers using microchip technology for respiratory disease research?
Researchers have developed a new technology that uses microchips to grow miniature copies of human lungs from human embryonic stem cells (hESCs). This approach enables the stem cells to organize themselves into complex “micro lungs” that mimic the intricacy of human lung tissue. It allows for high-throughput analysis of lung tissue infection, removing the variable factors that usually occur when using different patient samples.
What are the potential applications of this new technology?
This technology provides a unique way to study lung infections like COVID-19 and other diseases. It can also be used to screen potential drugs, study the susceptibility of alveoli cells to SARS-CoV-2, and determine how blocking certain signaling pathways can reduce infection susceptibility. Moreover, it is designed to be ready to respond rapidly to future pandemics.
How is the variability of patient samples reduced with this technology?
By cultivating genetically identical mini lungs from human embryonic stem cells (hESCs), the researchers can minimize the usual variability seen in patient responses. As these “micro lungs” share the same DNA signature, researchers can focus on the key variable — the virus.
What is the significance of using stem cells in this research?
Stem cells are the foundational cells of the human body. They can infinitely divide to create more stem cells or differentiate into any other tissue. By using stem cells, researchers can explore their potential in creating synthetic organs and tissues to model diseases and find therapeutic mechanisms.
How can this technology help in future pandemics?
This platform is designed to respond to future pandemics with greater speed and precision. It can be used to quickly develop therapies, and to screen for drugs, compounds, vaccines, and monoclonal antibodies directly in human tissue, thus potentially accelerating the response to new health threats.
More about Lab-Grown Miniature Lungs
- Understanding Stem Cells
- Microchips in Medicine
- Advancements in Respiratory Disease Research
- The Role of Stem Cells in Disease Modeling
- Cultivating Miniature Organs for Medical Research
