While “cures” are currently out of reach, researchers at the University of Washington’s Institute for Stem Cell and Regenerative Medicine (ISCRM) are hard at work studying degenerative conditions: diabetes, heart disease, Alzheimer’s disease, and kidney disease. These debilitating diseases result from the degeneration of tissues and organs. In some, the cells of the affected organ have died and new cells do not grow. For example, when a patient has a heart attack, heart cells die and a scar forms. Because the heart is not a regenerative organ, no new heart cells replace the dead cells. In other diseases, cells malfunction. This is the case in Alzheimer’s disease, in which the patient’s brain accumulates several toxic proteins. Medications can help manage some of the symptoms of these degenerative diseases, but they are currently not curable.
Regenerative medicine offers hope. Harnessing the potential of stem cells, it opens up the possibility of growing new cells and even replacement tissues and organs in the laboratory. Transplantation of these stem cell-derived tissues or organs to patients with degenerative diseases may one day extend life, if not providing a cure. ISCRMresearchers are engaged in the long journey of teasing out the molecular and cellular mechanisms that cause degenerative diseases, with the ultimate goal of developing therapies based on the power of stem cells. At this point, however no stem cell-derived tissues are ready to be tested in human clinical trials; it is still too dangerous.
The Institute brings together scientists from many different fields, including Neurology, Cardiology, Pathology, Bioengineering, Nephrology, Immunology, Endocrinology, and Rehabilitation Medicine, to name but a few. All of these researchers share a common interest in the characteristics of pluripotent stem cells (PSCs), how PSCs mature, and ultimately, how we can utilize PSCs to develop treatments for an array of degenerative diseases.
Embryonic stem cells are primitive cells found in the early embryo, typically a few days after the sperm impregnates the egg. Researchers around the world have derived embryonic stem cell lines from the embryos of many different species. We have learned how, under defined conditions, these cells can reproduce indefinitely, remaining in their primitive state. These cells are “pluripotent” — they have the potential to mature into many cell types found in the body.
Researchers have recently developed another type of stem cell: the induced pluripotent stem cell, or iPSC. A sample of a patient’s skin, urine, or blood is taken, then their adult cells are isolated, and induced to “devolve” and become “embryonic stem cell-like” – that is, pluripotent.
By adding various chemicals, and treating the iPSCs under very specific conditions, our researchers can then train the cells to mature and “differentiate” into different types of cells. These cells have the same genes – that is, the same DNA sequence – as the patient from whom the sample was obtained.
By exposing these artificially-created cells to various drugs, we can test therapies that the patient’s body may respond to. Our team is able to create neural cells from iPSCs for modeling Alzheimer’s disease, and test drugs for Alzheimer’s in this cell-based system. Using gene-editing tools, we can introduce mutations in the cells to mimic disease, or repair mutations that cause disease. In this way, we can compare drug responses in the lab and patients can avoid invasive biopsies.
The road to developing patient-ready therapies for debilitating diseases from stem cells is a long one. Placing pluripotent stem cells into the human body is dangerous. Early researchers thought this was a good approach, but we now know that the cells may not develop as expected. Because they are pluripotent, they can develop abnormally.
In the U.S., drugs used to treat diseases and medical conditions are regulated by the U.S. Food and Drug Administration. All must pass rigorous laboratory and human testing to demonstrate that they are safe and effective. The FDA oversees the clinical trials and reviews the results. Only after a tested product is deemed safe and effective will the FDA approve marketing of the product for treatment of the condition or disease for which it was tested.
Over the next decade, we are confident the Institute’s research will bring progress leading to new clinical trials.