Stem Cells and Induction of Lesion-Induced Neural Circuit Reorganization
Damage to the central nervous system (CNS) causes significant loss of function, reduced quality of life, and substantial cost to society. Damage can be caused by disease, stroke, or trauma. After CNS injury, there may be some recovery, which arises by the formation of new connections in the brain. An approach to improving recovery is to stimulate the mechanisms that form these new connections. Stem cell therapy is a promising avenue for promoting recovery of CNS function. An important goal of this area of research is to identify which stem cells are most effective and to understand how they promote recovery. An obstacle to achieving these goals is that lesions are variable and it is difficult to quantify the formation of new connections. We have developed a lesion model that takes advantage of a pathway containing large, distinct synaptic terminations. This model permits quantitative, robust assessment of lesion-induced sprouting. The lesion is highly reproducible and the number and precision of induced connections can be determined accurately. We propose to use this system to test the effectiveness of stem cell grafts. This model will enable us to compare different types of stem cells and characterize their effects on damaged tissue. Our approach will provide a way to understand the mechanisms by which stem cells effect tissue repair and ultimately lead to the development of new treatments for human diseases and disorders.
Central nervous system injury and stroke are the leading causes of disability in California. Current medical care relies on immediate treatment to lessen the extent of damage. However, there is no known cure that restores function. Stem cell therapy is a promising approach based on several studies in disease and injury models, but more information is needed on how stem cells work in promoting recovery. The proposed studies will provide a tool for assessing stem cell efficacy and for understanding mechanisms by which stem cells promote reorganization of neural circuits. The results will help identify optimal stem cell therapies that will alleviate effects of stroke and traumatic central nervous system injury in Californians. In addition, the project will create new jobs in California and stimulate the state’s economy. It will provide training in stem cell research to new trainees, who will further develop our knowledge in this area, and stimulate further interaction between academic institutions and biomedical technology.