Migration and bioscaffold interaction of induced pluripotent stem cell-derived human neural stem cells for neural regeneration
Spinal cord injuries (SCIs) are extremely debilitating conditions without an effective treatment. Several treatment plans are suggested that focus on replacement stem cells, implantable bioscaffolds, or a combination of the two. For such approaches, induced pluripotent stem cells (iPSCs) may be superior to other sources/types of stem cells that have some serious ethical and immunological issues associated with them. Collagen may be the most desirable biomaterial for scaffold construction as it is the most abundant protein in the extracellular matrix, readily biodegradable, and allows for easy cell attachment to its surface. Research suggests that soy protein isolates (SPIs) have an anti-inflammatory response that could prevent rejection of grafted materials, such as a scaffold, by its host. For this study, human iPSC neural stem cells were cultured and differentiated into neurons and oligodendrocyte precursor cells. These cells survived culturing in 3D hydrogels and within a type-1 collagen scaffold. Migration studies of iPSCs and neurons showed the ability of these cells to migrate within the gel, indicating that they could move to form functional connections with host tissue. Finally, a bioscaffold formed by SPI and collagen protein composite was fabricated and tested for its support of neuron growth and neurite extension. Cells were tested on different functional material coatings to characterize the biological function of SPI and collagen mixture. Proliferation of human microglial cells and iPS-derived neurons decreased in culture wells containing SPI but cells still migrated. This indicates SPI's ability to reduce an immune response from the host. The successful creation and testing of an implantable SPI-collagen scaffold seeded with iPSC-derived neural cells in an animal model of SCI could pave the way for similar treatment of human patients.
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This thesis is embargoed till the end of August 2020.