Year 2

A major goal of stem cell research is to generate various functional human cell types to promote repair or replacement in injury or disease. Our lab studies the repair of central nervous system after injury such as a spinal cord injury. We have been utilizing a fluorescent reporter line we developed with CIRM funding to derive and characterize human corticospinal motor neurons, a neuronal population that is damaged or lost in spinal cord injury and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). These neurons are of paramount importance to skilled voluntary movement in humans, the loss or damage of which leads to paralysis and disability. The goal for making a reporter line is that whenever the cells light up (literally), we will know what they have become the type of cells that we would wish to get. Following last year’s initial progress, we have made significant progress in this funding period. We found that our fluorescent reporter is useful in following the desired cell types throughout cell growth in culture dishes or after we introduce these cells into animal models by transplantation. We have performed experiments to validate the identity and usefulness of these cells. In culture, these cells exhibit the desired signature gene expression pattern, electrophysiological properties and morphologies as well. We will continue to improve our culture condition to maximize efficiency and purity. Meanwhile, we have transplanted these cells into the mouse brain to study them in the complex central nervous system because many of the properties cannot be studied in cell culture such as the connection of nerve cells to other brain area or spinal cord. We were excited to find that these cells, once transplanted, can survive, integrate into the mouse central nervous system, and send out long neuronal processes characteristic of endogenous nerve cells. Some of the projections appear to take the path of the projections of the corticospinal motor neurons, indicating that our approach will likely succeed. Thanks to CIRM’s support, we will continue to investigate the various parameters to improve our transplantation studies. Knowledge gained from this study will pave the way to make better disease-models-in-a-dish for neurological conditions such as ALS and to develop therapies for ALS, spinal cord injury, traumatic brain injury, stroke and other neurological conditions when corticospinal motor neurons are damaged of lost.