Long-term Organotypic Slice Model: A novel ex vivo culture system for the in situ study of stem cell and cancer cell biology in the brain and spinal cord

Funding Type: 
Tools and Technologies I
Grant Number: 
RT1-01109
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Novel applications for Stem Cell Therapy have been proposed for a broad range of congenital and acquired pathology. The Central Nervous System represents a key target for stem cell therapy. The central nervous system, comprised of the brain and spinal cord, has long been viewed as neither capable of clinically significant regeneration nor, unlike many other vital organs, amenable to reconstitution through transplantation. Stem cell therapy may provide the first meaningful approach for the reestablishment of neurological function in the setting of inherited or developmental absence, or in meaningful recovery after loss of function for addressing brain and spinal cord pathology. Malignant brain and spinal cord tumors remain a leading cause of seriousness and death for children and adults. Pediatric brain tumors are second only to leukemia as the most common malignancy of childhood and now represent the leading cause of cancer-related death in children. The prognosis for malignant brain tumors remains dismal, best appreciated in poor long-term survival statistics. Accumulating data document permanent functional disability exhibited by the fortunate survivors. New approaches to the treatment of brain tumors are desperately needed. New insight into the nature of cancer has resulted from the isolation and preliminary characterization of cancer stem cells from a number of malignancies including leukemia, multiple myeloma, squamous cell cancer, malignant melanoma, breast cancer, and in the brain: medulloblastoma, ependymoma and malignant glioma. The nature of their origins from their normal stem cell counterparts will provide invaluable new insights into the development of cancer, leading to novel treatment strategies. This proposal focuses on a new way of studying stem cells, including cancer stem cells that may lead to new insights into the development of brain and spinal cord cancers, leading to improved treatment.
Statement of Benefit to California: 
Malignant brain and spinal cord tumors remain a leading cause of morbidity and mortality for children and adults. Pediatric brain tumors are second only to leukemia as the most common malignancy of childhood and now represent the leading cause of cancer-related death in children. The prognosis for malignant brain tumors remains dismal, best appreciated in poor long-term survival statistics. Accumulating data document permanent functional disability exhibited by the fortunate survivors. The costs for the patient and family cannot be overestimated. Overall estimates of the incidence of brain cancers in the United States show that about 20,000 will be diagnosed annually with about 2500 in California. The economic costs are high. Repeated use of physician, inpatient, outpatient and laboratory services as well as lost future earnings and occurrence of secondary diseases cost Californians of more than 1.5 billion dollars annually. Fundamentally new approaches to the treatment of brain tumors are desperately needed. The objectives of this proposal focus upon utilizing a refined biological model to allow for the direct study of in situ behaviors of stem cell (neural stem cells, embryonic stem cells, induced pluripotent stem cells) and cancer stem cell populations within brain and spinal cord microenvironments with the ultimate goal being improved therapeutic applications.

© 2013 California Institute for Regenerative Medicine