Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.

These studies develop a stem cell therapy for vascular dementia and white matter stroke through late stage questions of clinical use in humans, using pre-clinical mouse models and cell culture models. In this latest reporting period, progress has been made on this issue of tumor formation. Extensive studies were completed to assess whether this cell type, termed human induced pluripotent stem cell-derived glial enriched progenitors (hiPSC-GEPS), can cause tumors after transplantation, or may contain a cell type in the preparation that might cause tumors. These studies found that the presence of undifferentiated pluripotent hiPSC is below 0.1%, and is safe to be transplanted in both males and females. Importantly, based on preliminary studies, the expected levels of hiPSC on the final hiPSC-GEPs therapeutic product we will be below 0.01% (10 hiPSC cell into 100000 hiPSC-GEP cells) and so this threshold of 0.1% will not be close to the range in the final product.

In addition to these tumorigenicity studies, studies in this reporting period developed a potency assay for hiPSC-GEPs. This assay determined the growth of new connections, termed axonal sprouting, that is induced by hiPSC-GEPs from neurons in culture, and the causative factors or proteins from hiPSC-GEPs that produce this axonal sprouting. Finally, in this reporting period, a Target Product Profile was written with the latest data and studies.