In Vivo Neuronal Reprogramming of Fibroblasts After Spinal Cord Injury

SUMMARY Neuron loss is a frequent result of spinal cord injury (SCI). A fundamental but unresolved challenge is how to restore the lost neurons and repair the neural circuits after SCI. Stem cell-based transplantation has limitations on immune compatibility, neuronal survival, and functional integration. The long-term goal of this proposal is to define a regenerative strategy by using a patient's own scar-forming cells without cell transplantation. In response to SCI, perivascular cells proliferate and migrate into the lesion core to form the fibrotic scar. Scar formation is initially beneficial by restricting damage but ultimately detrimental to neural regeneration through acting as a physical and chemical barrier to axonal regeneration and growth. The goal of this high risk but high reward project is to define methods to convert these fibroblasts into neurons. Aim 1 will focus on reprogramming of fibroblasts into progenitors in vivo. Stem cell factors will be examined. Aim 2 will focus on direct neuronal conversion of fibroblasts in vivo. Several key neurogenic factors will be examined for induction of neurons. Results of this work may reveal a regeneration-based therapeutic strategy by targeting the fibrotic scar after SCI.