Age-related diseases of the nervous system are major challenges for biomedicine in the 21st century. These disorders, which include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and stroke, cause loss of neural tissue and functional impairment. Currently, there is no cure for these devastating neurological disorders. A promising approach to the treatment of age-related neurological disorders is cell therapy, i.e., transplantation of nerve cells into the brain or spinal cord to replace lost cells and restore function. Work in this field has been limited however, due to the limited availability of cells for transplantation. For example, cells from 6-10 human fetuses obtained 6-10 weeks post-conception are required for one patient with Parkinson’s disease to undergo transplantation. Human embryonic stem cells (hESCs) offer a potentially unlimited source of any cell type that may be required for cell replacement therapy, due to their remarkable ability to self-renew (they can divide indefinitely in culture) and to develop into any cell type in the body.
Funded by CIRM, we have built out approximately 3400 square feet of shared laboratory space within our existing research facility for hESC research, as well as approximately 2400 square feet for classroom facilities dedicated to training in hESC culture and manipulation. Supported by this facility, we have in the past year successfully developed a process for the production of functional dopaminergic neurons from hESCs that are suitable for potential clinical uses, e.g., in treating Parkinson’s disease (Parkinson’s disease is caused by the death of dopaminergic neurons). Our system provides a path to a scalable Good Manufacture Practice (GMP)-applicable process of generation of dopaminergic neurons from hESCs for therapeutic applications, and a ready source of large numbers of neurons for potential drug screening applications. In addition, we have developed a screening strategy that allows us to rapidly identify clinically approved drugs for use in GMP protocol that can be safely used to deplete unwanted contaminating precursor cells from dopaminergic neurons, a target for cell therapy.
Before a hESC-based therapy can be developed, it is essential to train scientists to efficiently grow, maintain and manipulate these cells. We have taught two types of hands-on training courses in the past year with more than 30 scientists across California participated: a basic 5-day hESC culture course and an advanced 5-day hESC culture course, to meet the diverse needs of California scientists. These courses provided scientists with an understanding of hESC biology and enabled them to set up and conduct hESC research after completion of training.