The potential of pluripotent stem cells and the ability to scale and differentiate them to generate large numbers of enriched cell populations has created new opportunities and approaches to treat human disease. Preclinical proof-of-principle data demonstrates that stem cell-derived neural grafts can be used to reverse symptoms of multiple neurological conditions, including Parkinson’s Disease. Cell grafts enriched with dopaminergic neurons, can structurally and functionally integrate in the brain of Parkinson’s Disease models to reverse motor deficits, a finding which has launched several clinical trials. While the results in animal models is essential proof-of-concept, the survival and integration of these cells is suboptimal compared to treatments from fetal-derived ventral midbrain grafts.  An area of preclinical and clinical research showing promise in influencing neuronal survival and plasticity is exercise. The benefits of exercise on neural function and disease progression have been widely reported and they have also been shown to enhance the survival and integration of transplanted cells in models of some neurological diseases. However, there is limited data on the benefit of exercise on the functional outcomes of neural grafts in Parkinson’s Disease models. The guests on today’s program will discuss their recent study looking at the effect of exercise on cellular engraftment and functional recovery in animal models of Parkinson’s Disease and the implications for clinical outcomes.

Parent-specific epigenetic marks (imprints) leading to parent-specific gene expression are crucial for normal growth and development, yet their mechanisms of establishment and maintenance are not fully understood. In humans, approximately 200 imprinted genes have been discovered, and improper imprinting can manifest in growth restriction, obesity, intellectual disabilities, behavioral abnormalities, and an increased risk of certain cancers. While the use of pluripotent stem cells, especially those in the naïve state, have advanced aspects of modeling early development, a persistent issue hampering bona fide naïve hPSCs is the erosion of imprints. Our guests on today's episode will discuss genomic imprinting, its function, impact, and a new reporter system of imprinted gene expression in hPSCs that enables real-time visualization of loss-of-imprinting at single-cell resolution. This assay provides an important tool to help discover how to improve the imprint fidelity of naïve hPSCs and hence their application for studies of human development and regeneration.