Stem Cell Program

High Impact Priorities

The Stem Cell Program at Children's Hospital Boston has a single, driving focus: translate stem cell research findings into better treatments for children and adults around the globe. To this end, Program researchers are pursuing five high-priority clinical goals.

Create Customized Treatments:
Cell therapy’s great potential lies in creating healthy cells the patient’s body won’t reject. Children’s stem cell researchers lead in developing the technologies that will make this possible. They were first to transform mouse embryonic stem cells (ESs) into blood stem cells and among the first to show these cells can cure disease (in animals).

Today, the Stem Cell Program is one of the very few in the country applying these techniques to human cells. In addition, it has pioneered methods for turning a patient’s own cells back into immature stem cells. These reprogrammed cells are pluripotent, meaning they can potentially become any tissue needed for treatment or repair: bone, blood, or brain. Because they come from the patient’s own body, they have the potential to overcome tissue rejection issues.

Stem Cell Program researchers have now created these induced pluripotent stem cells (iPS cells) for more than a dozen diseases. Science, the world’s most widely read scientific journal, named cellular reprogramming the Breakthrough of the Year for 2008. Next steps for getting this potentially life-saving work to the clinic include: optimizing methods for creating large quantities of iPS cells; turning the iPS cells into the specific, more mature cells needed to treat a disease (e.g., blood stem cells to treat leukemia patients); and producing the cells under sterile conditions that meet federal standards for medical treatments.

Reverse Genetic Disorders:
Gene therapy seeks to conquer disease by inserting curative genes into defective cells. Since genes play a decisive role in many human illnesses, gene therapy has the potential to one day cure a broad range of deadly and disabling conditions, including blood diseases, muscular dystrophies, and cancers. However, getting the genes into the right places in the right cells in sufficient quantities to reverse disease has proven challenging.

Viruses are today’s gene delivery vehicles of choice because they are masters at invading human cells. However, they can land near and inappropriately activate cancer-causing genes or stimulate an immune system attack. iPS cells promise an improved method of gene delivery, as the genetically corrected cells can be evaluated before transplantation into patients. Derived from a patient’s own tissues, genetically corrected outside the body, transformed into the needed cell type, then transplanted back into the patient, they would replace the patient’s diseased cells with healthy ones. As Program researchers develop fundamental iPS cell technologies, they are also perfecting techniques for gene correction.

Detect and Defeat Cancer Stem Cells:
A small population of cells gives many cancers their lethal might. These 1-in-10,000 stem cells are self-renewing, spawn all other cells in a tumor and are often resistant to chemotherapy. Understanding how they form, how they are sustained and how to defeat them is among the most intensive areas of cancer research today.

Stem Cell Program researchers are honing in on the fundamentals of cancer stem cell biology, with exciting implications for treatment. They have, for example, discovered a protein that maintains cells in an immature and stem-like state and may be a master molecule of “stemness.” They have shown that this protein, LIN28, is abundant in embryonic stem cells and many cancers. The researchers are now searching for ways to inhibit LIN28, a promising new approach to cancer treatment. Still other Program researchers have isolated what may be a potent lung cancer stem cell, identified mechanisms that sustain leukemia and skin cancer stem cells, and launched innovative studies of how tissues know when to stop growing, a mechanism that goes off course in cancer. Each of these projects promises fresh approaches to defeating cancer.

Model Disease:
iPS cells move human disease into a Petri dish. Grown from patients with specific genetic disorders, they allow scientists to study the earliest events in the diseases’ development, providing insights that could spur new approaches to treatment. Children’s Stem Cell Program leads the world in generating disease-specific iPS cell lines. They have created them for dozens of diseases, including diabetes, Huntington disease, muscular dystrophy, and numerous blood disorders. They are making these cell lines available to other investigators and intensely studying them and in collaboration with researchers throughout the Children’s community.

This unprecedented resource will allow our scientists to ask such fundamental questions as: What aspects of tissue formation are faulty? What genes are involved? Are there proteins we can replace or pathways we can supplement to get healthy cells to form? The answers will build a knowledge base targeted to yield new treatments.

Discover New Drugs:
Children’s Stem Cell Program uses high-throughput robotics to screen thousands of chemicals in a search for drugs that will help turn pluripotent stem cells into the more mature cells needed to treat disease. In a stunning early success, our researchers discovered that an existing drug, called PGE2, boosts blood stem cell production four-fold—both during embryonic development and after the immune system has been damaged by chemotherapy. Its effect during development means PGE2 could be used to amplify lab-grown blood stem cells, a critical step in creating a viable cell therapy for blood diseases.

More immediately, PGE2 promises an effective solution to a serious drawback of blood stem cell transplantation. Cord blood is now frequently used for transplants but the number of blood stem cells within a single cord is frequently too small to stimulate full blood system recovery in adults or older children. As a result, patients receive stem cells from two cords. This poses a heightened risk of immune system complications because the cords are not genetically matched. PGE2 may boost the number of stem cells enough to make a single cord sufficient. Clinical trials are now underway in patients at Dana-Farber Cancer Institute and Massachusetts General Hospital.

Children’s stem cell researchers have discovered and are now investigating an additional five drugs that boost blood stem cell production. In addition, they have identified multiple new drug targets in their work on specific diseases, such as cancer, and are aggressively seeking chemicals that can be converted into treatments.

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