Abstract 130: Induced Neural Stem Cell Treated Stroke Pigs Show Improved White Matter Integrity and Brain Metabolism Post-ischemic Stroke

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Abstract

Recent studies in rodent stroke models have shown that induced pluripotent stem cell derived neural stem cells (iNSCs) can lead to a significant decrease in lesion size, immune response and improvement in functional deficits. These improvements are linked to the iNSC potential dual mode of action as they can perform as a cell replacement therapy and produce neuroprotective and regenerative signaling. These results are promising yet the vast majority of therapies developed in rodent stroke models have failed to translate in clinical trials; suggesting that iNSC therapy should be tested in a more human like model such as the pig. We hypothesize that iNSC treatment will lead to improved white matter integrity, brain metabolism and cerebral blood flow (CBF) as determined by magnetic resonance imaging and spectroscopy (MRI and MRS) in stroked pigs. Eight male landrace pigs underwent middle cerebral artery occlusion stroke surgery. After 5 days, 4 pigs received iNSCs intraparenchymal injections and 4 pigs received vehicle only injections. Pigs underwent MRI and MRS assessment at 24 hrs post-injury and 1, 4 and 12 wks post-injection. MRI results at 24 hrs showed that all pigs had an ischemic stroke. At 1 wk post-injection, fractional anisotropy measurements of white matter integrity showed the affected side of the brain was 71% and 52% of normal, non-treated and treated respectively. At 12 wks, iNSC treated pigs showed a significant improvement in FA at 93% of normal, while non-treated pigs showed no improvement. MRS results demonstrated a significant decrease in NAA, Cr and Cho at 1 wk post-injection in treated and non-treated pigs. However, treated pigs showed a significant improvement in NAA, Cr and Cho at 12 wks post-injection, while non-treated pigs showed no improvement. At 12 wks, ischemic tissue in iNSC treated pigs had trending increases in CBF, while non-treated pigs showed no improvement. These results demonstrated that iNSC treated stroke pigs show improved white matter integrity, brain metabolism and CBF post-ischemic stroke and that iNSCs may one day be a viable clinical option for human stroke patients.

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