Children with severe immune deficiencies cannot pet a cat, play in a sandbox or even hug a parent without risking life-threatening infection.

Luigi Notarangelo, MD, is one of many people using iPS cells to probe the biology of disease.

“Understanding the biology of these diseases is not simple,” says Luigi Notarangelo, MD, director of Children’s Research and Molecular Diagnosis Program in Primary Immunodeficiencies. “First of all, they are extremely rare. In addition, they are genetically heterogeneous. Each patient may have his or her own mutation even in the same gene.”

With iPS cells, Notarangelo can precisely model each patient’s genetic defect, and recapture the disease at its earliest beginnings. He is now collaborating with the Stem Cell Program to create iPS cells representing eight of the 14 variations of SCID, the most severe immune deficiency. Notarangelo will map the differing ways these variants hobble immune response and ultimately use the iPS cells to investigate drugs and other interventions that may reverse disease.

Spotlight

• Restoring immune function in mice

  Children’s Hospital Boston researcher George Q. Daley, MD, PhD, then at the Whitehead Institute, was the first to demonstrate, in 2002, that pluripotent stem cells could successfully treat immune deficiency in a mouse model when combined with gene therapy. The research team created genetically matched embryonic stem cells through nuclear transfer, introduced corrective genes, then derived healthy blood stem cells and infused them into the mice, partially restoring their immune function.

• Immune disorders at Children’s

  To learn more about how Children’s Hospital Boston can treat the wide range of immune system disorders, such as SCID, please visit our Immunology Program.

• Disease-specific iPS cells

  By creating iPS cells from patients with specific diseases, researchers can model that disease in a culture dish and observe its earliest beginnings. In 2008, the laboratory of George Q. Daley, MD, PhD, Director of Stem Cell Transplantation Program, reported creating a collection of iPS cell lines from patients with 10 different diseases. The lines are under active study at Children’s Hospital Boston, and are available to scientists around the world, housed at a core facility at the Harvard Stem Cell Institute. The Daley Lab has also taught scores of scientists how to make the cells themselves.