Year 4

Research supported by this CIRM grant focused on understanding the immune signaling that influences neural stem cells in the brain and spinal cord. Stem cells are important for the natural replacement of brain cells that may be lost due to age, disease, or injury. Stem cells may also be useful in repairing the brain.

Our research has shown that immune signaling and the tissue inflammation that accompanies injury or disease strongly inhibits “neurogenesis” or the production of new neurons from stem cells. Our goals in this work are to identify factors that naturally promote neurogenesis and apply these factors to enhance natural repair and/or improve the utility of stem cell transplants for therapy.

One of our strategies is to identify inhibitory factors produced by the immune system during tissue inflammation and develop better interventions to block these signals and promote neural circuit repair when an injury or disease process is present. As a result of the research supported by CIRM we have identified three novel uses for drugs that have already been used in clinical settings. These drugs increase the number of new neurons produced by stem cells in the brain by either blocking negative immune signals or by directly stimulating neurogenesis.

Experiments started in the final year of this grant will now continue in studies of stem cell transplants that are not perfectly matched to the recipient. Many cell transplant therapies for neurological disease or injury have utilized cells from another individual rather than a patient’s own cells. Tissue transplants are normally rejected by the immune system if they do not closely match the recipient and we have found that classical methods to protect grafted cells may not work as well as anticipated. Using the drugs identified in our CIRM funded research, we will next test whether controlling immune system effects can further improve the efficacy of stem cell therapies that have been engineered to treat stroke, spinal injury or Parkinson’s disease.