Research on Diseases

Heart DiseaseChildren’s pediatric cardiologist, William Pu, MD, and research fellow, Bin Zhou, MD, were the first to discover heart muscle cells could be derived from a type of cardiac progenitor called Wt1. In this image, Wt-1 cells expressing epicardial cells are tagged with a fluorescent red protein. Image courtesy of Drs. William Pu and Bin Zhou, Children's Hospital Boston.

Recent research at Children’s Hospital Boston has revealed that the heart has its own source of stem cells. In 2006, Stuart Orkin, MD, and Sean Wu, MD, PhD, of Children’s have shown that these heart stem cells can form two major types of heart cells: myocardial cells (the muscles that, together, contract to make the heart beat) and smooth muscle cells (the lining of the heart’s blood vessels). This finding gives researchers a better understanding of how the heart forms, and also boosts the idea of treating diseased or defective heart tissue with heart stem cells.

In 2008, Children’s researcher William Pu, MD an affiliate member of the Stem Cell Program, found another source of stem cells in the epicardium (the surface of the heart). Combined with work from Orkin and other researchers, Pu’s discovery completes a trio of genes – Wt1, Nkx2-5 and Isl1 – that, when active in a fetus, helps create blood vessels, myocardial cells and fibroblasts. Pu hopes this knowledge can be useful in future treatments for adult heart defects, using these stem cells to repair damaged hearts.

Pu is also using induced pluripotent cell (iPS) technology to understand how gene mutations can prevent the heart from growing normally, causing congenital heart defects. His lab is seeking to reprogram skin cells from patients with specific heart malformations to create iPS cells. These iPS cells will then be used to create heart muscle cells, and in the process, researchers can observe how heart diseases develop, from beginning to end. This knowledge can help doctors understand how those patients’ conditions started and how they may be able to treat them.

Related work by Bernhard Kuhn, MD, of Children’s Cardiovascular Program and an affiliate member of the Stem Cell Program at Children’s, is seeking to enhance the ability of heart muscle cells to regenerate without directly using stem cells. Kuhn recently found two separate molecules that may be used to stimulate heart muscle cell regeneration. These molecules are currently being tested in animal models of heart failure. Kuhn hopes to translate his findings into medicines to repair damaged heart tissue by using the heart’s own ability to heal.



  • Stuart Orkin and Sean Wu’s work with heart stem cells

    To read about Stuart Orkin and Sean Wu’s work with heart stem cells, check out this news release.

  • Read about William Pu’s work

    To read about William Pu’s past research on finding sources of heart stem cells, check out this news release.

  • Bernhard Kuhn’s experiments

    To read about Bernhard Kuhn’s experiments on regenerating heart cells, check out this news release.

  • Cellular reprogramming to create iPS

    Cellular reprogramming to create iPS cells was named Breakthrough of the Year for 2008 by Science magazine. For more information on Children’s Hospital Boston disease-specific lines of iPS cells, check out this news release and feature story.