Browsing by Subject "Department of Neurosurgery"
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Item Correction of Mucopolysaccharidosis Type I (MPS I) with Multipotent Adult Progenitor Cells (MAPCs) in an Immunodeficient Mouse Model(2010-04-21) Evavold, CarrieHurler Syndrome or Mucopolysaccharidosis I (MPS I) is an autosomal recessive lysosomal storage disease characterized by skeletal abnormalities, hepatosplenomegaly, and neurological degeneration. Children who exhibit MPS I lack α-L-iduronidase (IDUA), a crucial enzyme in the degradation pathway of glycosaminoglycans (GAGs), specifically heparan and dermatan sulfate. GAG accumulation in lysosomes interferes with normal cell function creating multi-systemic problems. Current treatments including enzyme replacement therapy and hematopoietic stem cell transplantation are not widely available and fail to correct the majority of symptoms, particularly mental retardation and skeletal anomalies. Using a NOD/SCID immunodeficient mouse model of MPS I, we attempted to correct the enzyme deficiency by transplanting human multipotent adult progenitor cells (MAPCs) directly into the striatum within five days of birth. Through the process of cross-correction, the IDUA enzyme released from the transplanted cells is taken up by the defective cells. The efficacy of the MAPCs was investigated through measurement of IDUA levels in different tissues, immunohistochemical staining, and sensorimotor testing. The transplanted MAPCs were detected throughout the central nervous system along with decreased levels of GAGs indicating sufficient delivery of IDUA to the cells. Sensorimotor coordination on a rotarod test improved in the MAPC-treated MPS I mice compared to untreated MPS I mice. These results denote that transplantation of MAPCs into the striatum greatly reduces GAG tissue levels in the brain and ameliorates sensorimotor function in MPS I mice.Item Interview with Shelley Chou(University of Minnesota, 1999-07-12) Chou, Shelley N.; Pflaum, Ann M.Ann Pflaum interviews Dr. Shelley Chou, former vice-president for Health Sciences and head of the Department of Neurosurgery.Item Vaccine-based immunotherapy for glioblastoma using tumor cells, Zika virus, and a checkpoint inhibitor(2020) Guo, Winston L.; Chrostek, Matthew R.; Toman, Nikolas G.; Tran, Sarah K.; Crane, Andrew T.; Low, Walter C.Glioblastoma multiforme (GBM), the most common malignant brain tumor, is very aggressive with a survival rate of less than 5% at five years, despite the current treatment regimen comprised of surgical resection, radiation therapy, and chemotherapy with temozolomide. New and more effective cancer treatments may stem from immunotherapies, which amplify and modify the immune response to target tumor cells. These immunotherapies include checkpoint inhibitors, vaccines, and oncolytic viruses. When used as standalone treatments for GBM, they moderately promote survival and remission. However, combinations of immunotherapies may act synergistically. This project aims to generate a more effective treatment for GBM that employs dual immunotherapies: a checkpoint inhibitor and a cancer vaccine. In a GL261 mouse model of malignant gliomas, we found that this combination yields an overall survival of 75%, compared to a survival rate of 25% with the vaccine alone. Our results suggest that the additional checkpoint inhibitor attenuates tumor-driven immunosuppression and improves survival without apparent toxic effects. While this may encourage the addition of more immunotherapies into a single treatment for GBM, closer evaluation of chemotoxicity is necessary before a finalized treatment is viable for clinical trials. Nonetheless, our findings demonstrate the promising efficacy of combining immunotherapies.