%0 PDF %T Synthetic and Nature-derived Lipid Nanoparticles for Nerve Regeneration %A Takeda, Yuji. %8 2017-04-19 %R http://localhost/files/2227n162v %X Abstract: Regenerative medicine is a promising approach for the treatment of nerve injuries. Soluble growth factors are commonly used to promote neuronal cell proliferation and differentiation. However, there remain some issues associated with the use of growth factors alone. Exosomes are lipid nanovesicles secreted by many types of cells and used for intercellular communication. Since exosome contains RNA and proteins, they could be a useful alternative to growth factors for promoting tissue regeneration. We hypothesized that exosomes derived from differentiating cells provide clues about the active components promoting cell differentiation and proliferation. In this thesis, we used PC12 cells, a neuronal cell line as a model. We investigated the role of exosomes derived from PC12 cells at various stages of neuronal differentiation in promoting the differentiation of mesenchymal stem cells (MSCs) towards a neuronal lineage. After the treatment with exosomes, MSCs developed a neuron-like morphology, and the gene and protein expressions of neuronal markers were upregulated. Microarray and proteomics analyses identified active components including miRNAs and proteins that play a role in neurite extension and neuronal differentiation. These results suggest that the exosome may be delivering necessary signals, such as RNA and protein molecules, involved in functional nerve regeneration. In addition, we took the first step in building exosome mimics using synthetic lipid-based nanoparticles with defined miRNA cargo to induce neuronal differentiation of MSCs. We performed screening assays to optimize the chemical structure of bioreducible lipids for miRNA delivery. Then, we used the optimal lipid to deliver miR-9, a known signaling molecule in neuronal differentiation, to MSCs. We observed that the delivery of miR-9 induced morphological changes and upregulation of neuronal marker genes in the MSCs. We believe these lipid nanoparticles, exosomes and bioreducible lipids, have potential applications for nerve tissue regeneration.; Thesis (Ph.D.)--Tufts University, 2016.; Submitted to the Dept. of Biomedical Engineering.; Advisor: Qiaobing Xu.; Committee: David Kaplan, Shoji Takeuchi, and Emmanuel Tzanakakis.; Keywords: Biomedical engineering, Molecular biology, and Cellular biology. %[ 2022-10-11 %9 Text %~ Tufts Digital Library %W Institution