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.
Understand and control microenvironment impact on chronic liver disease progression. We TRANSLATE technologies and knowledges into solutions for drug development, diagnostics and therapeutics.
Quantitative analysis of the dynamic process of liver regeneration and chronic liver diseases.
Investigating the contraction and propagation mechanism of secretory lumen such as bile canaliculi.
Developing novel and useful biomaterials, cell sources, and analytics for long-term maintenance of highly functional epithelial cells in culture.
Developing robust, scalable, low cost and predictive in vitro drug and toxin testing platforms.
Respect : every TMBL 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 TMBL 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).
Yu Y., Ananthanarayanan A., Singh N.H., Hong X., Sakban R., Mittal, N., Luo, X., Robens J., Xia L., McMillian M., and Yu H. (2018) TGFβ1-mediated suppression of Cytochrome P450(CYP) induction responses in rat hepatocyte-fibroblast co-cultures . Toxicology In Vitro, August 2018; 50: 47-53. DOI: 10.1016/j.tiv.2018.01.015
Co-culture of hepatocyte and fibroblasts has shown distinct advantages in enhancing certain liver specific functions and maintaining hepatic polarity. However, the utility of hepatocyte co-culture models for studies, such as drug-drug interaction studies, has not been completely elucidated. In this study the induction of Cyp1a2, Cyp2b1/2, and Cyp3a2, the three major cytochrome P450 (CYP) isoforms in the rat liver, was evaluated in randomly mixed co-cultures and micropatterned co-cultures. We found that in both co-culture configurations, the drug-induced Cyp1a2, Cyp2b1/2, Cyp3a2 mRNA and activity were suppressed relative to those in monocultured hepatocytes. Further, we observed a significant increase in TGFβ1 production in the co-cultures. Addition of 100 pg/ml TGFβ1 to hepatocyte monocultures resulted in the suppression of Cyp1a2, Cyp2b1/2, and Cyp3a2 induction. These findings implicate TGFβ1 as one of the important factors impairing drug induced CYP induction in co-cultures and suggests that caution needs to be exercised in the use of hepatocyte-fibroblast cocultures for CYP induction studies.
Toh, Y.C., Raja, A., Yu, H., and van Noort, D. (2018) A 3D microfluidic model to recapitulate cancer cell migration and invasion. Bioengineering, 5(2): 29. DOI: 10.3390/bioengineering5020029
We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1) in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis). It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.
Luo, X., Gupta, K., Ananthanarayanan, A., Wang, Z., Xia, L., Li, A., Sakban, R., Liu, S., and Yu, H. (2018) Directed Differentiation of Adult Liver Derived Mesenchymal Like Stem Cells into Functional Hepatocytes. Scientific Reports, 8: 2818. DOI: 0.1038/s41598-018-20304-5
Shortage of functional hepatocytes hampers drug safety testing and therapeutic applications because mature hepatocytes cannot be expanded and maintain functions in vitro. Recent studies have reported that liver progenitor cells can originate from mature hepatocytes in vivo. Derivation of proliferating progenitor cells from mature hepatocytes, and re-differentiation into functional hepatocytes in vitro has not been successful. Here we report the derivation of novel mesenchymal-like stem cells (arHMSCs) from adult rat hepatocytes. Immunofluorescence and flow cytometry characterization of arHMSCs found expression of mesenchymal markers CD29, CD44, CD90, vimentin and alpha smooth muscle actin. These arHMSCs proliferated in vitro for 4 passages yielding 104 fold increase in cell number in 28 days, and differentiated into hepatocyte-like cells (arHMSC-H). The arHMSC-H expressed significantly higher level of hepatocyte-specific markers (200 fold for albumin and 6 fold for Cyp450 enzymes) than arHMSCs. The arHMSC-H also demonstrated dose response curves similar to primary hepatocytes for 3 of the 6 paradigm hepatotoxicants tested, demonstrating utility in drug safety testing applications.