(596al) Transdifferentiation of Mesenchymal Stem Cells on Micropatterned Polymeric Substrates

Peripheral nerve injuries are cause of serious neurological disorders and can result in paralysis and sensory/motor dysfunctions. Schwann cells (SCs) can enhance myelin production capabilities for insulating neuronal axons which may also help to improve the motor function of the damaged nervous tissue. Researchers in our group and elsewhere have extracted Schwann cells and seeded them in conduits and have shown that they facilitate and enhance nerve regeneration in various animal models. However, there is no good source of Schwann cells, and they have to be obtained by sacrificing a healthy nerve which may result in donor site morbidity. Additionally, since SCs are not easy to maintain in a cell culture environment, we are focusing on producing cells having SC like phenotype using adult stem cells. Mesenchymal stem cells (MSCs) are multipotent cells capable of transdifferentiating into various cell types including a Schwann cell like phenotypes. The focus of this work is to transdifferentiate MSCs into SC-like phenotypes using micropatterned polymer substrates. Micropatterning has been used for aligning various cell types in the past, and our hypothesis is that alignment would promote transdifferentiation into SC-like phenotypes. We have shown that MSCs align themselves in the direction of microgrooves when grown on micropatterned substrates. As a proof of principle, we have used polystyrene (PS) films for testing the transdifferentiation of MSCs and their alignment, as PS is biocompatible and a good substrate for cell culture. Immunocytochemistry experiments have been done on the MSCs grown on PS films to determine the alignment and transdifferentiation into SC-like phenotypes. The transdifferentiated cells align along the microgrooves, which can help the regenerating axons grow in particular directions. In the future, we are going to use FDA approved biodegradable polymers, which could be engineered into a conduit and can be inserted at the site of damaged nerve to promote peripheral nerve regeneration.