The lymphatic system provides a slow flow of fluid from our organs and tissues into the bloodstream. It returns fluid and proteins that leak from blood vessels, provides passage for immune and inflammatory cells from the tissues to the blood, and hosts key niches for immune cells. How this system develops hasn’t been well understood, but now researchers from the Perelman School of Medicine at the University of Pennsylvania have found from experiments in mice that the early flow of lymph fluid is a critical factor in the development of mature lymphatic vessels.

“Once the primary lymph vessels are in place, an enormous amount of maturation has to happen, and what we’ve found is that the maturation process is triggered by physical forces from the earliest flow of lymph fluid in a developing embryo,” said senior author Mark L. Kahn, MD, the Edward S. Cooper, M.D./Norman Roosevelt and Elizabeth Meriwether McLure Professor in the department of Medicine.

The findings, published online ahead of the August issue of the Journal of Clinical Investigation, represent a big step forward in the basic scientific understanding of lymphatic system development. They also should contribute to a better understanding of lymphatic disorders, including the lymphedema that affects many women following breast cancer surgery.

Mice With No Lymph Flow

The project was prompted in part by recent studies of cultured lymphatic vessel endothelial cells that suggested that fluid forces could be an important factor in the maturation of lymphatic vessels. But there was no straightforward way to test this hypothesis in live animals.

“No one had been able to come up with a way to stop lymph flow in embryonic animals, without preventing their lymphatic vessels from developing in the first place,” said first author Daniel T. Sweet, PhD, a postdoctoral fellow in the Kahn Laboratory.

In humans and other mammals, the lymphatic system is a low-flow system that, unlike the blood circulatory system, has no central pump. Instead it relies on muscular contraction of the mature lymphatic vessel wall and small valves in lymphatic vessels to squeeze fluid along and prevent backflow.

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