Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93334
標題: 微流體技術於神經幹細胞應用之發展
Development of microfluidic platforms for neural stem cell research
作者: 林璟暉
Ching-Hui Lin
關鍵字: Microfluidics;Neural stem/progenitor cells;neurosphere;single-cell;monoclonal culture;微流體;神經幹細胞;神經球;單細胞;單株化培養
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摘要: 
In this study we aim to develop new platforms for neurosphere assay and single cell manipulation for neural stem/progenitor cell (NSPC) research. The microfluidic cell dissociation platform is designed for enzyme-free dissociation of neurospheres into single-cells. Neurosphere assay is a common method for identification of neural stem/progenitor cells, but obtaining single cells from dissociated neurospheres is difficult using non-enzymatic methods. Our microfluidic chip approach that utilizes flow and microstructures to dissociate neurospheres. Results show that this microfluidic-chip-based neurosphere dissociation method can generate high yields of single cells from dissociated neurospheres of two mouse NSPC models (KT98 and DC115) for 90% and 95%, respectively. The microfluidic chip dissociated cells had high viabilities (80–85%) and the ability to re-grow into neurospheres, demonstrating the applicability of this device to neurosphere-assay applications. In addition to the self-renewal capability, the dissociated cells also retained their normal differentiation potentials, as shown by their capabilities to differentiate into three neural lineages (neurons, astroglia, and oligodendrocytes) when cultured in differentiation culture conditions. Furthermore, neurospheres consist of heterogeneous cell populations including multipotent NSPCs, and lineage immature neuronal and glial precursors and has been shown by the spatial distribution of more differentiated (GFAP+ and TuJ1+) cells at the core and surrounded by the stem cells (Nestin+). The microfluidic cell dissociation platform provides the capability for label-free enrichment of NSPCs from dissociated neurospheres. We demonstrate that the microfluidic chip processed cells show significantly higher NSPC properties such as more SOX2 and FGF1 expression, proliferation rates and neuronal differentiation potential compared to unprocessed cells.
Studying the heterogeneity of single neural cells is crucial but technical difficult. Therefore we develop a cell manipulation method for high-efficiency single cells loading in large microwells. We report the development and application of a dual-well microfluidic device with high-yield of single-cell loading (~77%), long-term single-cell clonal culture capability (7 days) and heterogeneity analysis using single-cell colony formation assay. The high single-cell loading yield is achieved by using sets of small microwells termed 'capture-wells' and big microwells termed 'culture-wells' according to their utilities for single-cell capture and clonal culture respectively. This novel device architecture allows the size of the 'culture' microwells to be flexibly adjusted without affecting the single-cell loading efficiency making it useful for cell culture applications.
We envision that our microfluidic platforms are simple and reliable tools for neural stem/progenitor cells manipulation with high-efficiency and high-throughput properties. In addition to the above advantages, the processed cells from our microfluidic platforms are easy to be used with conventional cell analysis and culture methods for further NSPC investigation and applications.
URI: http://hdl.handle.net/11455/93334
Rights: 同意授權瀏覽/列印電子全文服務,2015-08-20起公開。
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