The Gladstone Institutes conducts basic and applied research in stem cell biology and regenerative medicine. It explores how stem cells are created and controlled, the mechanisms by which they are regulated, and how they evolve into specialized cells.
Induced Pluripotent Stem Cells
Gladstone scientists study how human skin cells can be reprogrammed into induced pluripotent stem (iPS) cells, and they are working to refine the production of these cells. Recently, they described new methods that overcome barriers to increasing the quality and quantity of iPS cells, including using cocktails of small molecules, or chemicals, that boost the reprogramming process.
Other researchers at Gladstone explore ways to turn human iPS cells into different cell types in the body, such as heart, brain, liver, pancreas, and bone cells. With these cells, they are learning how organs develop and how they become damaged by disease. These insights will help researchers find new ways to prevent, treat, or cure diseases. In addition, scientists are working to identify the molecules that instruct iPS cells to adopt a certain state, which could improve their use for regenerative medicine.
Direct Cellular Reprogramming
Gladstone is at the forefront of direct cellular reprogramming, a process that changes the identity of a cell without it first passing through an intermediate or pluripotent state. For example, cells that form scar tissue in a mouse heart have been directly reprogrammed into heart muscle cells. This ground-breaking research could lead to a novel way to repair heart damage after a heart attack using a patient’s own cells by converting them within the organ into new muscle. Human skin cells have also been directly converted into neurons that can be used to study and find treatments for diseases in the brain, as well as liver cells and insulin-producing cells of the pancreas.
Reprogramming Through Chemical Biology
Traditional methods for reprogramming cells use genes that encode proteins called transcription factors, which bind to DNA to turn genes in the cell on and off. In a revolutionary set of studies, Gladstone scientists pioneered a way to reprogram skin cells into heart cells and brain cells using only a combination of chemicals and without adding any external genes to the cells. This research lays the groundwork for one day being able to regenerate lost or damaged cells in the body with a drug.
Human Disease Modeling
Gladstone investigators are creating human iPS cells derived from patients’ skin cells to discover the genetic and biological causes of disease. Using a unique, automated robotic microscope that can follow a single cell over days or weeks, the scientists track the birth, maturation, and death of neurons afflicted with Alzheimer’s, Huntington’s, and Parkinson’s diseases and ALS.
Other researchers are using CRISPR to engineer the genomes of heart cells created from the iPS cells of patients with cardiovascular disorders to study the genetic causes of the cardiomyopathies and congenital heart defects.
Cells do not work in isolation; they are connected in intricate networks to form tissues and organs. Gladstone scientists are engineering tissues from stem cells to create better models of human disease. The researchers are using these three-dimensional models to study disease, screen drugs, and mimic aspects of healthy, diseased, or injured tissues.