Engineers Tackle Growing Threat of Infectious Diseases

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According to their research, the model can be manipulated to recreate the process of immune-cell response and reproduce the function of the lymph nodes in immune cell activation.

Scott Adams, creator of the “Dilbert” comic strip, once said: “Normal people... believe that if it ain’t broke, don’t fix it. Engineers believe that if it ain’t broke, it doesn’t have enough features yet.” Although Adams cleverly captures the innovative spirit of engineers—he developed “Dilbert” after working with engineers at the Pacific Bell telephone company in the 1980s and 1990s—even he probably wouldn’t believe how some engineers have applied their unique knowledge and skill sets to solve seemingly intractable problems in infectious diseases.

Indeed, one such group, from the lab of Ankur Singh, PhD, at the Sibley School of Mechanical and Aerospace Engineering at Cornell University, partnered with colleagues at Cornell’s Meinig School of Biomedical Engineering and Weill Cornell Medicine to create what they describe as a 3-D modular immune organoid designed to replicate the anatomical structures found within the lymph nodes and mimic the early stages of immune response. According to the team’s study published in a December issue of ACS Biomaterials: Science and Engineering, the model can be manipulated to recreate the process of immune-cell response and reproduce the function of the lymph nodes in immune cell activation. Another study on aspects of the project was also published in December in the journal Nature Protocols.

In a recent interview with Contagion, Dr. Singh commented on his team’s research. “There is a massive increase in infectious disease outbreaks, including the recent Ebola and ongoing Zika threats,” he said. “We do not fully understand how the human body responds to these rapidly mutating viruses and evolving pathogens. Conventional bench-side research and clinical therapeutic development rely on animal sources, and existing 2-D systems do not represent what’s inside your body, which is a dynamic 3-D space that undergoes remodeling post infection. This is a fundamental advance.”

Dr. Singh and his colleagues note that their 3-D organoid model is designed to foster faster replication of B cells, in much higher quantities than existing 2-D models. With the organoid, researchers can modify immune organs following infection, to tailor and control immune-cell response and cell-cell interactions, as well as other functions. Made from a synthetic polyethylene glycol or semisynthetic gelatin-based platform, the organoid also provides bench researchers with an efficient method for replicating the microenvironment of a germinal center, the structures within lymphoid tissues that develop following B cell activation, in response to infection. To date, the mechanisms underlying this response have not been fully understood; however, the new organoid, as living tissue, will allow researchers to model processes that, until now, they have not been able to recreate in vivo.

“This is really a neat, designer technology where you can plug-and-play biological signals,” Dr. Singh said. “Tailored immune organoids will [provide] researchers and clinicians the ability to identify factors that have the potential to rapidly boost immunity. We hope this technology will enable rapid, higher-throughput translation of immunotherapeutics.”

Dr. Singh and his colleagues are not done with this organoid just yet. He told Contagion that his team is already working to expand the organoid technology to “address the urgent unmet need in the field of infection and autoimmune diseases, transplant rejection, and cancers.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.

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