Laboratory of Cellular and Tissue Engineering

Vision.

We share the VISION of EDUCATING ambitious young scientists and engineers to make impacts beyond individual efforts through team projects and collaborative learning in academia and industry.

Research Mission

Understand and control liver regeneration and chronic disease progression. We TRANSLATE technologies and knowledges into solutions for drug development, diagnostics and therapeutics.

Research Goals

Quantitative analysis of the dynamic process of liver regeneration and chronic liver diseases.

Investigating the formation and dynamic maintenance of inter-cellular tissue space such as bile canaliculi and sinusoids that define liver functions.

Developing novel and useful biomaterials, cell sources, and analytics for long-term maintenance of highly functional liver cells in culture.

Developing robust, scalable, low cost and predictive in vitro drug and pathogen testing platforms.

Shared Values

Respect : every LCTE member is important and yet consciously sensitive to other members and the collective impacts. Decisions incorporate inputs from all the stakeholders for fairness and transparency.

Professionalism: every LCTE member strives to attain ever higher quality and standard of her/his own work through mutual empowerment, critique and support to each other.

No-walls culture: solutions to real-life problems can never be confined within artificially-created boundaries (organizational, disciplinary, cultural, inter-personal, or mental inertia).

Featured Recent Publications

Fong, L.S.E., and Yu, H. (2017) Organs-on-chips: Filtration enabled by differentiation. Nature Biomedical Engineering, 10 May 2017; 1(5):0074. DOI: 10.1038/s41551-017-0074

The efficient generation of mature podocytes from induced pluripotent stem cells makes possible the recapitulation of renal blood filtration on a chip.

Fang, Y., Zhuo, S., Qu, Y., Choudhury, D., Wang, Z., Iliescu, C., and Yu, H. (2017) On Chip Two-photon Metabolic Imaging for Drug Toxicity Testing. Biomicrofluidics, May 2017; 11(3): 034108. DOI: 10.1063/1.4983615

We have developed a microfluidic system suitable to be incorporated with a metabolic imaging method to monitor the drug response of cells cultured on a chip. The cells were perfusion-cultured to mimic the blood flow in vivo. Label-free optical measurements and imaging of nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence intensity and morphological changes were evaluated noninvasively. Drug responses calculated using redox ratio imaging were compared with the drug toxicity testing results obtained with a traditional well-plate system. We found that our method can accurately monitor the cell viability and drug response and that the IC50 value obtained from imaging analysis was sensitive and comparable with a commonly used cell viability assay: MTS (3–(4,5-dimethylthiazol-2-yl)–5–(3-carboxymethoxyphenyl)-2–(4-sulfo-phenyl)-2H-tetrazolium) assay. Our method could serve as a fast, non-invasive, and reliable way for drug screening and toxicity testing as well as enabling real-time monitoring of in vitro cultured cells.

Gupta, K., Li, Q., Fan, J.J., Fong, E.L.S., Song, Z., Mo, S., Tang, H., Ng, I.C., Ng, C.W., Zhuo, S., Dong, C.-Y., Low, B.C., Wee, A., Dan, Y.Y., Kanchanawong, P., So, P., Viasnoff, V., and Yu, H. (2017) Actomyosin Contractility Drives Bile Regurgitation as an Early Response During Obstructive Cholestasis. Journal of Hepatology, 18 March 2017; S0168-8278(17): 30061-30062. DOI: 10.1016/j.jhep.2017.01.026

BACKGROUND & AIMS: A wide range of liver diseases manifest as biliary obstruction, or cholestasis. However, the sequence of molecular events triggered as part of the early hepatocellular homeostatic response in obstructive cholestasis is poorly elucidated. Bile canaliculi are dynamic luminal structures that undergo actomyosin-mediated periodic contractions to propel secreted bile. Additionally, pericanalicular actin is known to accumulate during obstructive cholestasis. Therefore, we hypothesize that the pericanalicular actin cortex undergoes significant remodeling as a regulatory response to obstructive cholestasis.
METHODS: Investigations into the effects of obstructive cholestasis were performed in a bile duct ligated mouse model. To elucidate the role of actomyosin contractility, we used sandwich-cultured hepatocytes transfected with various fluorescently labeled proteins and pharmacological inhibitors of actomyosin contractility.
RESULTS: We report here that actomyosin contractility induces transient deformations along the canalicular membrane, a process we have termed inward blebbing. We show that these membrane intrusions are initiated by local ruptures in the pericanalicular actin cortex; and they typically retract following repair by actin polymerization and actomyosin contraction. However, above a certain osmotic pressure threshold, these inward blebs pinch away from the canalicular membrane into the hepatocyte cytoplasm as large vesicles (2-8 μm). Importantly, we show that these vesicles aid in the regurgitation of bile from the bile canaliculi.
CONCLUSION: Actomyosin contractility induces the formation of bile-regurgitative vesicles, thus serving as an early homeostatic mechanism against increased biliary pressure during cholestasis.
LAY ABSTRACT: Bile canaliculi lumen undergoes cyclic expansion and contraction mediated by bile secretion, and resistance from the surrounding actin bundles. Further expansion due to bile duct blockade leads to the formation of inward blebs and vesicles which carry away excess bile to prevent bile build up in the lumen.