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Our researchers are committed to learning all we can about these diseases in order to make sure these children have the best shot at living as normal a life as possible — and stem cells may be the key.

A few examples of our work with stem cells for genetic diseases includes:

  • using iPS cells to model genetic blood diseases and discover new treatments
  • studying genetic disorders that cause heart failure and arrhythmias using organ-on-a-chip technology
  • gene-correction and cell-replacement toward cures for congenital blindness

Genetic blood diseases

Stem cells are helping doctors at Boston Children's Hospital understand different facets of genetic blood disorders, including those that lead to bone marrow failure (BMF) and leukemia. At Boston Children’s, stem cell biologists are using induced pluripotent cell (iPS cells) from mature body cells from patients with genetic BMF syndromes, such as Dyskeratosis congenita (DC), Diamond Blackfan anemia (DBA), Fanconi anemia (FA), Pearson syndrome (PS) and Shwachman Diamond syndrome (SDS). These BMF disorders predispose to cancer, and are associated with defects throughout the body. In close collaboration with Boston Children's clinicians and physician-scientists, studies by Stem Cell Program investigators using patient iPS cells are revealing disease mechanisms underlying the failure of blood and other organ-specific stem cells, and uncovering new therapeutic possibilities for not only the blood defects and cancer risk, but to treat other organ defects as well.

Congenital heart diseases

Scientists are exploiting the capacity of iPS cells to give rise to a variety of cell types and structures, to tackle congenital diseases of the heart and other organs. Pluripotent stem cells can be converted into a large range of specific cell types, that can be used to mimic the complex structure and properties of organs like the heart. In this way, problems in the communication and arrangement of multiple cells in a tissue can be better understood. These can include congenital arrhythmias, abnormalities in the conduction of electrical signals across heart muscle; and cardiomyopathies in which the cardiac muscle fibers are disorganized and cannot contract effectively.

Congenital blindness

Stem Cell Program scientists are combining powerful genome editing technologies with patient-specific stem cells to create new opportunities for personalized medicine. Congenital disorders of blindness can result from progressive deterioration of the retina. Patient-derived iPS cells have been converted into retina cells for treatment in patients, but in the case of congenital blindness these cell would still carry the genetic mutation. To address this, the Stem Cell Program’s Stem Cell Core led by Thorsten Schlaeger, PhD, generated iPS cell lines to model the genetic retinal diseases Leber Congenital Amaurosis (LCA) and X-Linked Retinoschisis (XLRS). Schlaeger’s team used CRISPR-Cas9 mediated genome editing to precisely repair the disease-causing mutations in several LCA and XLRS patient-derived hiPSCs. Using a very efficient and precise genome editing technique called Cas9 Base Editing, they were able to repair the mutant gene in over 50% of XLRS patient derived hiPSCs.

Research on immune disorders

Several genetic blood diseases can prevent the body from producing a healthy immune system. Patients with severe combined immunodeficiency (SCID) can die from infections that healthy children easily fight off. The best treatment for these diseases is a bone marrow transplant. Bone marrow contains hematopoietic stem cells, which differentiate into various blood cells including the B cells and T cells needed for a healthy immune system.

Stem cell scientist George Q. Daley, MD, PhD, has led his team in creating dozens of lines of induced pluripotent cells (iPS), including lines derived from patients with SCID. Studying these iPS cells in the lab will give scientists a chance to see how these patients’ respective diseases develop, and how the diseases can be treated.