In the U.S., liver associated diseases are major contributors to morbidity and mortality. Approximately 40,000 people in the U.S. die each year from acute or chronic liver diseases. Liver tissue engineering has made significant progress towards the creation of in vitro liver models for drug screening, as well as in vivo constructs for addressing the large clinical need for transplant sources. However, cell sourcing remains a significant challenge for both in vivo and in vitro liver models. Human induced pluripotent stem cells (iPSCs) are a promising technology in regenerative medicine as they can be autologously derived, maintain high proliferative capacity, and demonstrate enormous differentiation potential, while also mitigating the ethical concerns associated with the use of embryonic stem cells (ESCs). However, the application of iPSCs towards functional in vitro tissue models is still largely under development, and tissue-engineered constructs for in vivo transplantation have yet to be fully realized. To address these challenging issues, we propose to develop a functional in vitro micro-liver model via encapsulation of pre-differentiated iPSCs using a novel 3D bioprinting technique. This model will be subsequently enhanced through the addition of physiologically related components (i.e. co-cultures with supportive cells) to provide an advanced liver-on-a-chip model that can be studied further. The liver associated functions of the liver-on-a-chip models will be systematically examined.
In Specific Aim 1, we will develop a liver-on-a-chip model by encapsulating iPSC-derived hepatic progenitor cells within 3D biomimetic scaffolds.
In Specific Aim 2, we propose to incorporate biologically related supportive cell types into the liver on-a-chip model. To accomplish our goal, we have assembled the collaborative talents of three experts, including Chen for biofabrication and tissue engineering, Wang for iPSCs, and Feng for hepatocellular function and liver biology. We envision that our patient specific liver-on-a chip model can be explored as a reliable and cost-efficient in vitro platform to facilitate drug metabolism studies, preclinical drug screening, and fundamental hepatology research.

Public Health Relevance

This project seeks to develop a functional in vitro micro-liver model via encapsulation of pre-differentiated Human induced pluripotent stem cells using a novel 3D bioprinting technique. Such model can facilitate drug metabolism studies, preclinical drug screening, and fundamental hepatology research.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB017876-02
Application #
8737901
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Hunziker, Rosemarie
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biomedical Engineering
Type
Schools of Arts and Sciences
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Hribar, Kolin C; Soman, Pranav; Warner, John et al. (2014) Light-assisted direct-write of 3D functional biomaterials. Lab Chip 14:268-75