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Grand Challenges Grant Supports Tissue Engineered Model of Lymphatic System

Posted on May 28, 2013
Lymphatic on a Chip2

The Gates Foundation award to assistant professor J. Brandon Dixon will support development of a model lymphatic system on a microfluidic chip like this one

The Georgia Institute of Technology has announced that it is a Grand Challenges Explorations winner, an initiative funded by the Bill & Melinda Gates Foundation. J. Brandon Dixon, an assistant professor in Georgia Tech’s George W. Woodruff School of Mechanical Engineering, will pursue an innovative global health and development research project, titled “Lymphatic on a chip as a model for lymphatic filariasis (LF) parasites.”

Grand Challenges Explorations (GCE) funds individuals worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. Dixon’s project is one of the Grand Challenges Explorations Round 10 grants announced May 21 by the Bill & Melinda Gates Foundation.

To receive funding, Dixon and other Grand Challenges Explorations Round 10 winners demonstrated in a two-page online application a bold idea in one of four critical global heath and development topic areas that included agriculture development, neglected tropical diseases and communications.

The grant will fund development of a tissue-engineered model of the human lymphatic system that will support laboratory research into lymphatic filariasis, a parasitic disease known to cause elephantiasis. According to the World Health Organization, the mosquito-borne disease affects more than 120 million persons in tropical areas of the world, and can cause severe disfigurement. The parasitic worms that cause lymphatic filariasis are difficult to study because the most common species of the parasite can survive only in humans. While less common species can be maintained in felines or gerbils, they are challenging to culture long-term outside the host. The model that Dixon plans to develop would use human cells housed within fabricated microfluidic devices to closely simulate the environment where the adult worms live within their hosts, allowing the parasites to be studied longer term in vitro.

“We would use this human lymphatic environment on a microfluidic chip to study the progression of the disease and the communication between the host and the parasite,” explained Dixon, who is also a member of Georgia Tech’s Institute for Bioengineering and Bioscience. “We could also scale this up to evaluate new pharmaceutical compounds that could potentially target the worm.”

The microfluidic system will include human lymphatic endothelial cells, which are the primary cell type in contact with the worms in the body. Researchers will also include human dermal fibroblasts – an important cell type in the skin where the mosquito first delivers the parasitic infection – and the immune cells that fight infection long-term. Beyond creating the cellular environment needed to support the worms, the researchers will also design a matrix to house the living cells, determine which hormones and nutrients are needed, and establish appropriate fluid flow rates for the microfluidic devices to recreate the hydrodynamic forces the worms encounter in the body. The devices will be integrated into an optical platform that would allow researchers to quantify the activity of the worms over extended periods of time using automated image analysis algorithms.

Beyond studying lymphatic filariasis, Dixon believes a lymphatic system on a chip could ultimately support broader areas of research into disorders of this bodily system. The human lymphatic system has historically been underappreciated and is challenging to study because it is difficult to image, the vessels involved are small and the flow rates are very low compared to blood vasculature.

Source: Georgia Institute of Technology

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