UofL-led research shows substances in red grapes induce intestinal stem cells that provide protection from colitis


    LOUISVILLE, Ky. – A team of researchers from the University of Louisville has shown red table grapes produce substances that enable intestinal stem cells in mice to continue functioning even as colitis is introduced into their intestinal tract. The substances are the first exosome-like nanoparticles identified from an edible plant; until now, exosome nanoparticles have only been seen in mammals.

    The research is published online today (June 11, 2013) in the Nature Publishing Group’s journal Molecular Therapy.

    UofL scientist Huang-ge Zhang, D.V.M., Ph.D., and other colleagues at UofL, the Louisville Veterans Administration Medical Center, University of Alabama at Birmingham and Kansas State University isolated the grape exosome-like nanoparticles or GELNs, which are tiny vesicles that only can be seen under an electron microscope. The GLENs were administered orally to a group of mice in the laboratory. Another control group of mice did not receive GELNs.

    Colitis was then chemically induced in both groups over the course of several days. Within 13 days, there was 100 percent mortality of the control group. However, it took almost twice as many days – 25 – to see 100 percent mortality of the GELN-fed group.

    The researchers also found that when they stopped administering chemically induced colitis to a group of mice at day 9, they witnessed a rapid decrease in the rate of mortality in the GELN-fed group, eventually halting it altogether.

    “We know that self-renewal of the epithelium – the lining – of the intestine is essential to protect animals from disease, and this protection is driven by the intestine’s own stem cells,” Zhang said. “Withdrawing administration of the chemically induced colitis signified that the GELNs were acting upon the intestinal tract to protect itself from disease.”

    The researchers colored the GELNs with a fluorescent dye so they could observe them as they passed through the intestinal tract. “We could see that the GELNs stayed in the small intestine longer – about 12 hours or so – than in the large intestine,” Zhang said.

    Zhang holds the Founders Chair in Cancer Research at the James Graham Brown Cancer Center and is a professor in the Department of Microbiology and Immunology in UofL’s School of Medicine. He takes a common-sense approach in determining his research focus: He looks at what our ancestors ate.

    “The choices we make in selecting fruits and vegetables to eat today were passed down from generation to generation as favorable and nutritious for the human body,” he said. “So it makes sense for us to consider that eatable plants could help induce our own stem cells to protect us from disease.”

    This isn’t the first time Zhang has identified nanoparticles in plants. In May, another research team he helped lead uncovered a way to create nanoparticles using natural lipids from grapefruit and showed how the grapefruit-derived substances can be used to deliver therapeutic agents with fewer adverse effects than drugs that are contained in synthetic lipids.

    As was the case with his research using grapefruit, the grapes he used were the same type consumers buy every day, he said. “We purchased California grapes from area stores – Wal-Mart, Kroger, Meijer and others. They were not specially grown for us. We didn’t even use organic grapes,” he said.

    While the research is promising, he emphasized that it is early, basic research. “It may not hurt most people to increase their consumption of grapes, but they should know that we have much more work to do before we can definitively say what quantities and types can help prevent disease,” Zhang said.

    “I do believe we have opened up a brand new avenue of research. It is conceivable that other types of cells can take on GELNs, and we can possibly see their positive effects in other diseases such as cancer.”

    The research was supported in part by grants from the National Institutes of Health, Louisville Veterans Administration Medical Center Merit Review Grants and the Susan G. Komen Breast Cancer Foundation.

    Jill Scoggins is Director of Communications at UofL's Louis D. Brandeis School of Law. She has been at UofL since 2010.