BOSTON (ASRN.ORG)- A team of researchers at Massachusetts General Hospital Center for Engineering in Medicine has found the first evidence of cell-to-cell communication by amino acids, the building blocks of proteins, rather than by known protein signaling agents such as growth factors or cytokines.

"We were taken by complete surprise," says Rohit Jindal, PhD. "Past reports have implicated various growth factors and the extracellular matrix proteins secreted by other cell types in regulating hepatocyte behavior, but to the best of our knowledge, this is the first evidence that cells can communicate by changing local amino acid concentrations."

The development of a three-dimensional model of liver tissue in which hepatocytes (liver cells) are embedded in a layer of collagen and covered with a layer of endothelial cells - the cells that line blood vessels, which permeate the liver. In this model system liver cells recovered their metabolic activity much faster than in previous models - in two days instead of a week or longer. The fundamental discovery was that the amino acid proline was responsible for this enhanced recovery. A building block of collagen, proline was secreted by the endothelial layer of the liver model, taken up by hepatocytes and used to synthesize new collagen, leading to faster recovery of hepatocyte activity.

"The idea that one cell type could have a profound effect on the metabolism of neighboring cells by changing the local amino-acid concentration is fascinating" says Martin Yarmush, MD, PhD. "The liver is the body's central hub of amino acid, carbohydrate and lipid metabolism, and our basic understanding of such interactions will hopefully lead to strategies for better controlling liver function."

Yaakov Nahmias, PhD, adds, "It's not currently clear whether this mechanism occurs in living animals, but it could contribute to active liver remodeling during liver development or regeneration."  Arno Tilles, MD, and Francois Berthiaume, PhD noted that work was supported by grants.

 

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