Stem Cell Control

Cell Control
Stem cells, with their remarkable abilities to self-renew and to differentiate into multiple tissue lineages, hold great promise for regenerative medicine. In a developing embryo or an adult body, the fate of stem cells is tightly regulated by their microenvironments which provide a unique combination of various extracellular stimuli such as soluble factors, extracellular matrix proteins, cell-cell interactions, mechanical stress, pH, ionic strength, temperature, etc. Successful clinical applications of stem cells will require reproducing key signaling cues that govern self-renewal, proliferation, and differentiation of stem cells in vitro. Whereas conventional cell culture methods provide limited means to investigate extracellular cues, micro/nano technologies can offer a wide spectrum of tools to apply such cues to stem cells in a controlled manner. Therefore, stem cell research is likely to significantly benefit from a micro/nano technology-based platform that allows for screening combinations of various extracellular cues. In addition, the screening process for enabling combinations will be challenged by a large multi-dimensional parameter space created by the number and intensity of possible cues, requiring an efficient optimization method. Currently, we are developing novel engineering methods to control the fate of stem cells toward successful translation into regenerative medicine.

References
  1. Valamehr, B., Tsutsui, H., Ho, C.M., and Wu, H., "Developing Defined Culture Systems for Human Pluripotent Stem Cells," Regenerative Medicine, Vol. 6, pp. 623-634, 2011.
  2. Tsutsui, H.*, Valamehr, B.*, Hindoyan, A., Qiao, R., Ding, X., Guo, S., Witte, O.N., Liu, X., Ho, C.M., and Wu, H. “An Optimized Small Molecule Inhibitor Cocktail Supports Long-term Maintenance of Human Embryonic Stem Cells,” Nature Communications, 2:167, DOI: 10.1038/ncomms1165, 2011.

Biomedical Microdevices

microdevices
Interfacing with DNAs, proteins, and cells at their corresponding length scale can significantly enhance engagements of medical devices with these clinically relevant biological targets. Biomedical microdevices, typically integrating micro- and/or nano-scale transducers, can offer several advantages over the conventional methods, including small footprints, minimal samples and reagents consumption, ultrasensitive detection, and quick analyses. These advantages collectively make biomedical microdevices an ideal platform to develop implantable devices and point-of-care diagnostic tools for patients monitoring and treatments. Currently, we are focusing on developing platform technologies for advanced medical diagnostics and tissue culture.

References
  1. Tsutsui, H., Yu, E., Marquina, S., Valamehr, B., Wong, I., Wu, H., and Ho, C.M., “Efficient Dielectrophoretic Patterning of Embryonic Stem Cells in Energy Landscapes Defined by Hydrogel Geometries,” Annals of Biomedical Engineering, Vol. 38, pp. 3777-3788, 2010.
  2. Lillehoj, P.B., Tsutsui, H., Valamehr, B., Wu, H., and Ho, C.M., “Continuous Sorting of Heterogeneous-Sized Embryoid Bodies,” Lab on a Chip, Vol. 10, pp. 1678–1682, 2010.
  3. Tsutsui, H., and Ho, C.M., “Cell Separation by Non-Inertial Force Fields in Microfluidic Systems,” Mechanics Research Communications, Vol. 36, pp. 92-103, 2009.

Self-Assembling Biomaterials

selfassembly
Nature presents amazing self-assembling phenomena and impressive complex functions thereof, including molecular crystals, myosin fibers, cell membranes, tissues, weather patterns and many more. Whereas self-assembly has been studied and used as a novel approach to fabricate relatively simple products in nanometer scale, where conventional top-down fabrication methods are inefficient, its full potential has yet to be realized, especially in the area of three-dimensional, multiscale, hierarchical fabrications. We are investigating biomimetic self-assembly of various molecular components toward development of new functional biomaterials.

References
  1. Hsu, N., Latterman, P., Tong, M., Tran, C., Wu, A., Ziv, M., and Tsutsui, H., "Self-Assembled Organic Microwires as a New Biosensor Platform," BMES 2011 Annual Fall Meeting, 2011.

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