Neurodegenerative diseases comprise a broad spectrum of acute and chronic conditions in which the structure or functions of neurons are progressively lost, leading to their death. Acute neurodegenerative diseases include ischemic stroke and traumatic brain and spinal cord injury. Chronic neurodegenerative diseases include Parkinson’s disease, amyotrophic lateral sclerosis “Lou Gehrig's disease”, and Alzheimer’s disease among many others. Stem cell-based approaches hold tremendous hope to restore neuronal function in neurodegenerative disease. Transplantation of stem cells in animal models of neurodegenerative disease has been proven to restore neuronal function to some extent. However, significant barriers still exist to responsively translate stem cell-based approaches into treatments for human neurodegenerative diseases. We need to further investigate the action of stem cells after transplantation. In particular, one of the underrepresented areas in this research field is the effect of inflammation on transplanted stem cells. Notably, neurodegenerative diseases are accompanied by inflammation. Inflammation damages neurons as well as transplanted stem cells. This proposal attempts to find a way to reduce the damage to stem cells by inflammation to enhance the ability of stem cells to regenerate neuronal functions after transplantation. This project will help to discover new approaches to improve stem cell-based therapies for various neurodegenerative diseases.
Human stem cells hold great potential for regenerative medicine to treat many progressive neurodegenerative diseases such as Parkinson’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, and spinal cord injuries, to name just a few. These devastating neurodegenerative diseases are the leading causes of death and disability in the State of California. The progressive nature of these diseases with increasing disability is a burden on the patients, their families, and the State of California in both human suffering and healthcare costs. The goal of this project is to study the molecular changes within human neural stem cells (hNSCs) transplanted in neurodegenerative diseases in order to discover means to increase the regenerative capacity of transplanted hNSCs. This mechanistic and translational approach to characterize transplanted hNSCs will provide possible therapeutic strategies and clinical applications for neurodegenerative diseases, providing hope for the development of stem cell based therapies. Therefore, successful completion of this research will greatly benefit Californians suffering from neurodegenerative diseases and in need of such treatments, and have a tremendous impact on quality of life for the patient, his or her family, and for the economic and emotional burden on the State of California and its citizens.