"Generation of iPSCs from Human Foreskin Fibroblast for Transplantation with Embryonic Olfactory Ensheathing Gila into a Rat Model to Cure Spinal Cord Injury"
Host lab: Giles W. Plant
Stanford University
Spinal cord injury (SCI) results in a long-term functional deficit, as the injured spinal cord fails to connect to their original targets and restore circuitry. After the injury, many spinal cord cells are lost not only in the initial injury, but in the hours, days and weeks following the accident. In particular, neurons are also lost close to the injury site. Valuable therapies are extremely important for curing SCI. The Plant lab focuses on repairing spinal cord injury by performing stem cell and glial cell transplantation into injured spinal cord. These models are both mouse and rat. Recent studies in the lab showed that both human mesenchymal precursor cells (hMPCs), olfactory ensheathing glia (OEG) and Schwann cells (SC) are beneficial for the spinal cord after injury, especially the acute damage. Transplanted mesenchymal stem cells not only modulate the host immune response to injury and also direct neural stem cells and progenitors to differentiate along the linage which support regeneration. The Schwann cells encourage nerves to grow, while olfactory ensheathing glia provides help to ensure axons can grow out of the graft and back to the spinal cord.
My research goal is to introduce induced pluripotent stem cells to the lab for building another therapy in repairing injured spinal cord. The previous research showed that embryonic olfactory glia (eOEG) works better than Schwann cells, neonatal olfactory ensheathing glia (nOEG) and adult olfactory ensheathing glia (aOEG) in remyelinating focal areas of spinal cord demyelination. Some research also tried to co-transplant NSCs with OEGs or co-transplant neural progenitors (NPs) with Schwann cells (SCs) to provide better conditions for cells to differentiate into functional cell types and be more efficient for spinal cord injuries repair. In this study, we will co-transplant iPSCs with eOEGs and use iPSCs as the material for regeneration of nerve fiber. Embryonic OEGs will function for bridging cysts and scars, and guiding iPSCs into the lesion site in rats’ spinal cord injuries model. We have already successfully generated iPSCs from human foreskin fibroblasts by using the single lentiviral stem cell cassette produced by Mostoslavsky’s lab, which contains the four factor genes, Oct4, Sox2, Klf4 and cMyc. Injured Central Nervous System model that performed successfully in Plant’s lab will be used to determine whether embryonic olfactory glia will be better suited for this study. Animal behavior test, such as cylinder test and open field test, and Immunohistofluoresence analysis for the spinal cord tissue will be used to test the function and lesion recovery. This study will provide a new strategy for spinal cord injury repair. More studies can be performed to reduce tumor risk and optimize the strategy in the future.