Program Leader: Les E. Silberstein, MD

HSCI's mission of "taking out" key diseases would be impossible to achieve without mechanisms to reach the clinic. One of these is The Center for Human Cell Therapy (CHCT). Located at the Immune Disease Institute (IDI) and led by Leslie Silberstein, MD, of Children's Hospital, CHCT was established to provide an infrastructure to rapidly translate novel cell therapy protocols from the laboratory to the clinic and facilitate bench-to-bedside development of cellular therapies. HSCI scientists work with the CHCT to understand what needs to be done to meet regulatory requirements, develop pre-clinical and clinical trial protocols, and work with the FDA and other regulatory bodies to bring therapies to the clinic.

The Stem Cell Patch

Every year, one in every 2,500 children in the United States is born with a condition called congenital diaphragmatic hernia, in which the diaphragm does not close completely during fetal development, allowing some organs to migrate into the chest cavity. Typically, the opening is closed with a Teflon patch shortly after birth, and often must be replaced as the child grows. However, stem cell research may lead to a more enduring solution—a "stem cell patch" grown from mesenchymal stem cells (AMSCs) isolated from the mother's amniotic fluid prior to the child's birth that, unlike the Teflon version, can grow with the child.

This novel approach, led by pediatric surgeon Dario O. Fauza, MD, is quickly being moved toward the clinic with the help and guidance of the CHCT. Currently, HSCI is funding a study in large animals with the goal of conducting a study in people within a year. So far results have been positive, showing that the AMSC-based graft can repair the damage and continue to grow with the animal, making further operations unnecessary.

As this project approaches the milestone of first-inhuman clinical trials, Fauza has a vision of what might lie beyond. "I believe that transplants' days are numbered ... The fact that you would need a patient to die or to donate part of his or her body to save somebody else is a wonderful gift, but that will never cover the needs of the population. What we've seen so far allows us to have realistic expectations that tissue engineering in our lifetime will eventually be a substitute for transplantation techniques."

Fauza is working on addressing additional types of neonatal defects testing the right combination of cell type, material, structure, and growth environment for the specific applications. In addition to solving critical clinical needs, this work shows how multiple scientific disciplines need to interact and collaborate, how resources and know-how need to be leveraged, and how the clinic and the laboratory need to inform each other if stem cell therapies are to move forward effectively and efficiently.

Other Projects

Recent work by HSCI Executive Committee chair Leonard Zon, MD, of Children's Hospital, has led to a Phase I clinical trial with the CHCT to test a drug that has been shown to expand the number of hematopoietic stem cells in cord blood. If successful, this might mean that only one unit of cord blood would be necessary for reconstituting an adult immune system. This drug was first identified as a result of a screening project in zebrafish, demonstrating how the use of relevant live animal models can accelerate the process of moving to the clinic. Another project now in the CHCT lab is the result of an HSCI seed grant that focused on the use of mesenchymal stem cells as drug delivery vehicles to address human brain tumors.

In another step in moving fundamental technology toward clinical application, researchers at the Whitehead Institute and HSCI reported successfully reducing symptoms in a Parkinson's disease rat model by using dopamine-producing neurons derived from reprogrammed adult skin cells. This significant experiment demonstrated for the first time that reprogrammed cells have the ability to integrate into the neural system and positively affect neurodegenerative disease. In the coming year, we expect many more such experiments as we apply the multiple disease-specific cell lines and types that we can now create to in vitroand in vivomodels, hastening the time that we can bring such therapies to people.