Artificial cellular microenvironments to control cellular functions
Cellular microenvironmental cues (i.e., soluble factors, extracellular matrices (ECMs), and cell-cell interactions) have critical roles in determining stem cell fates. Conventional macro-scale techniques can only provide limited control of niches over cells; therefore, there is a need to develop tools that can accurately and effectively help in regulating stem cells.
Microfluidic technologies are advantageous compared to conventional 2D culture/experimental settings for investigating of the underlying mechanisms of niche roles on cells and tissues, as well as the establishment of in vitro cell-based assays, due to their ability to control liquid flow at a fL scale, create 3D geometry at nm to µm scales, minimize reagent/sample consumption, and to automate experimental procedures. In light of such unique features of microfluidic technology, while we could manipulate chemical treatments alone (i.e., drug candidates, growth factors, pH and gases), for most of cell-based assays, microfluidic technology offers the opportunity to regulate physical cellular conditions (i.e., pressure, shear stress, and tension) within a tiny space, in addition to the chemical treatments. Importantly, microfluidic devices allow cell culture and assays to be performed in a robust and high-throughput fashion within a single device, with dramatically reduced costs. These characteristics make microfluidic technology stand out as an ideal cell experimental system, and microfluidic technology would be the most suitable platform to recreate in vivo niche conditions and to systematically investigate unsolved niche mechanisms.
Previously, I have successfully developed high-throughput microfluidic platforms to create multiple 3D artificial cellular environments and to identify the optimal environments for cellular functions of interests via screening. By utilizing this platform, we will screen artificial cellular microenvironments that facilitate the differentiation process for targeted tissue cells derived from hPSCs.
I would like to emphasize that our results will be used to establish new methodologies for precisely induced hPSC differentiation as well as future hPSC applications in tissue engineering and regenerative medicine.
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- Integrated Heart/Cancer on a chip to reproduce the side effects of anti-cancer drug in vitro, K. Kamei,* Y. Kato, Y. Hirai,*, S. Ito, J. Satoh, A. Oka, T. Tsuchiya, Y. Chen and O. Tabata, RSC Advances, 7, 36777-36786 (2017); DOI: 10.1039/C7RA07716E (*Corresponding authors)
- Microfluidic-nanofiber hybrid array for screening of cellular microenvironments, K. Kamei‡*, Y. Mashimo‡, M. Yoshioka, Y. Tokunaga, C. Fockenberg, S. Terada, M. Nakajima, T. Shibata-Seki, L. Liu, T. Akaike, E. Kobatake, E. S. How, M. Uesugi and Y. Chen*, Small, 13(18), 1603104 (2017); DOI: 10.1002/smll.201603104 (*Corresponding authors; ‡These authors contributed equally to this work.)
- Characterization of phenotypic and transcriptional differences in human pluripotent stem cells under two- and three-dimensional culture conditions, K. Kamei*, Y. Koyama, Y. Tokunaga, Y. Mashimo, M. Yoshioka, C. Fockenberg, R. Mosbergen, O. Korn, C. Wells and Y. Chen*, Advanced Healthcare Materials, (2016);
- Directing and boosting of cell migration by the entropic force gradient in polymer solution, T. Fukuyama, A. Fuke, M. Mochizuki, K. Kamei and Y. T. Maeda, Langmuir 31(46), 12567–12572 (2015); DOI: 10.1021/acs.langmuir.5b02559
- 3D printing of soft lithography mold for rapid production of polydimethylsiloxane-based microfluidic devices for cell stimulation with concentration gradients, K. Kamei*, Y. Mashimo, Y. Koyama, C. Fockenberg, M. Nakashima, M. Nakajima, J.J. Li and Y. Chen*, Biomed. Microdev. 17(2), (2015); DOI: 10.1007/s10544-015-9928-y (*Corresponding authors)
- Phenotypic and transcriptional modulation of human pluripotent stem cells induced by nano/microfabrication materials, K. Kamei,‡* Y. Hirai,‡ Y. Makino, M. Yoshioka, Q. Yuan, M. Nakajima, Y. Chen, and O. Tabata,* Advanced Healthcare Materials, 2(2), 287-291 (2013); DOI: 10.1002/adhm.201200283 (*Corresponding authors; ‡These authors contributed equally to this work.)
- Integrated and diffusion-based micro-injectors for open access cell assays, X. Li, L. Liu, L. Wang, K. Kamei, Q. Yuan, F. Zhang, J. Shi, A. Kusumi, M. Xie, Z. Zhao and Y. Chen, Lab Chip, 11(15), 2612-2617 (2011)
- Microfluidic Image Cytometry for Quantitative Single-Cell Profiling of Human Pluripotent Stem Cells in Chemically Defined Conditions, K. Kamei,† M. Ohashi, E. Gschweng, Q. Ho, J. Suh, Z. T. F. Yu, J. Tang, A. T. Clark, A. D. Pyle, M. A. Teitell, K.-B. Lee, O. N. Witte and H.-R. Tseng,†, Lab. Chip, 10(9), 1113-1119 (2010) (†Corresponding authors)
- An integrated microfluidic culture device for quantitative analysis of human embryonic stem cells, K. Kamei*,S. Guo*, Z. T. F. Yu*, H. Takahashi, E. Gschweng, X. Wang, C. Suh, J. Tang, J. McLaughlin, O. N. Witte, K.-B. Lee and H.-R. Tseng, Lab. Chip, 9(4), 555-563 (2009) (*These authors contributed equally to this work.)
- An integrated microfluidic chip for parallel culture and multiparametric analysis of murine and human cells, Z. T. F. Yu*, K. Kamei*, H. Takahashi, C. J. Shu, G. W. He, R. W. Silverman, C. G. Radu, O. N. Witte, K.-B. Lee and H.-R. Tseng, Biomed. Microdev., 11, 547-555 (2009) (*These authors contributed equally to this work.)