In previous studies we identified novel non-hematopoietic umbilical cord blood stem cells (nh- UCBSCs) that could be expanded to high passages and exhibit restorative properties following ischemic brain injury repair. We found that the high passaged cells were equivalent, if not even better, than the low passaged nh-UCBSCs. This finding suggests that these cells can serve as a source of highly expandable cells that can be manufactured under controlled conditions for potential therapeutic applications. In this Phase I/II proposal we intend to scale-up production of nh-UCBSCs under good manufacturing practice (GMP) conditions at the GMP facility located on the campus of the University of Minnesota. These GMP manufactured cells will then be tested for efficacy using small animal (laboratory rat) and large animal (non-human primate) models of ischemic brain injury. In consultation with the FDA we are proposing IND-enabling studies to further qualifying these cells for use in a future clinical study. We will evaluate the safety and potential tumorigenicity of these cells, evaluate mechanisms of action and effects of cryopreservation. The results from this study will provide key data required by the Food and Drug Administration for an IND to conduct a clinical trial on the use of these cells in the treatment of ischemic brain injury.
Public Health Relevance Statement: Narrative We have identified a highly expandable non-hematopoietic stem cell population within human cord blood and evaluated its neuroprotective efficacy in laboratory rats with ischemic brain injury. The goal of the present application is to scale-up the production of these stem cells under good manufacturing practices (GMP), and evaluate the effectiveness of these cells in treating ischemic brain injury in rats and non-human primates to gather data needed to begin clinical trials.
Project Terms: acute stroke; Address; Animal Model; Animals; Biodistribution; Biological Markers; Blood; Blood Cells; Brain; Brain Stem Neoplasms; CD34 gene; Cell Line; cell type; Cells; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Consultations; Cryopreservation; Cyclic GMP; Data; Development; Doctor of Philosophy; Dose; Effectiveness; efficacy testing; Ensure; Evaluation; Exhibits; FDA approved; Future; Goals; Hematopoietic stem cells; Hour; Human; human stem cells; Image; Immune system; in vivo imaging; Infusion procedures; injury and repair; Intravenous; Ischemic Brain Injury; Ischemic Stroke; Laboratory Rat; Measures; Mesenchymal Stem Cells; microbial; Minnesota; Modeling; Molecular; Mononuclear; Natural Killer Cells; nervous system disorder; Nervous System Physiology; nonhuman primate; novel; optimal treatments; Phase; Population; post stroke; preclinical efficacy; Procedures; Process; Production; Property; Publishing; Qualifying; Rattus; Rodent; Rodent Model; Safety; scale up; Source; stem cell population; stem cell therapy; Stem cells; Stroke; stroke model; stroke patient; stroke therapy; Stroke Volume; Suggestion; Testing; Therapeutic; Therapeutic Effect; Toxic effect; treatment effect; Treatment Efficacy; Tumor Stem Cells; Tumorigenicity; Umbilical Cord Blood; United States Food and Drug Administration; Universities
