Texas A&M University research team develops a new organ-on-chip to model conditions that impact the lymph system.

Currently, there is little research focused on understanding mechanisms and drug discovery of lymphatic vascular diseases. However, conditions such as lymphedema, a build-up of fluid in the body when the lymph system is damaged, impact more than 200,000 people every year in the US alone. There is currently no cure for lymphedema and so treatment focuses on reducing the swelling and preventing complications such as lymphangiosarcoma which limits life expectancy to less than two years.

Longevity.Technology: Ask people to think of a circulatory system and hearts and arteries spring to mind; however the lesser-known lymph system is also a network of vessels, tissues and organs that are found throughout the body. Packed with white blood cells, lymph is a clear, watery fluid that plays an important role in the body’s immune response, helps to maintain a balance of bodily fluid and plays a part in the absorption of fats and fat-soluble nutrients. As effective as our blood circulation system is, water, proteins and other molecules leak constantly out of our capillaries pooling in the surrounding body tissues. The lymphatic system drains this excess fluid, preventing it from building up and causing swelling and damage.

Organ-on-chip (OOC) technology can mimic human organs in vitro, this enables faster and more economic drug development, as well as garnering insights into human health. OOC also means research can avoid animal models, instead obtaining human-specific, tissue-level and organ-level data in vitro. OOC research has included kidney, liver, airway, blood-brain-barrier and heart, and DARPA has supported the engineering of an instrument that links fluidically multiple OOCs together to create a body-on-chip, allowing research to be undertaken to understand how drugs impact multiple organ systems.

OOC hold great promise for regenerative medicine, from replacing damaged tissues and organs to induced pluripotent stem cells differentiation. OOC tech has been used to regenerate injured central nervous system neurons [1] and construct endothelialized human myocardium to aid an unhealthy heart [2] and can be used to build a specific human model, allowing for personalised preventative strategies and tailored therapies.

Dr Abhishek Jain, assistant professor in the Department of Biomedical Engineering at Texas A&M University, has taken his OOC expertise and applied them to the lymph system, creating the first lymphangion-chip.

To engineer this new organ-on-chip device, Jain’s team first developed a new technique to create microfluidic cylindrical blood or lymphatic vessels consisting of endothelial cells, which line blood vessels. Using this technique, the researchers then created a co-cultured multicellular lymphangion, the functional unit of a lymph vessel, and successfully recreated a typical section of a lymphatic transport vessel in vitro.

“We can now better understand how mechanical forces regulate lymphatic physiology and pathophysiology,” Jain said. “We can also understand what are the mechanisms that result in lymphedema, and then we can find new targets for drug discovery with this platform [3].”
The organ-on-chip project is in collaboration with Dr David Zawieja from the Texas A&M College of Medicine and the research was published the journal Lab on a Chip.

“Collaborations with Dr Zawieja and others in the department played a crucial role,” Jain said. “They introduced me to this topic and provide their longstanding expertise that has made it possible for us to create this new organ-on-chip platform and now advance it in these exciting directions using contemporary experimental models [3].”

Jain said the impact of this work is far-reaching because there is a new hope for patients with lymphatic diseases. They can now learn about the biology of these diseases and reach a point where they can be treated.

“The most exciting part of this research is that it is allowing us to now push the organ-on-chip in directions where finding cures for rare and orphan diseases is possible with less effort and money,” Jain said. “We can help the pharma industry to invest in this platform and find a cure for lymphedema that impacts millions of people [3].”