The liver, the largest internal organ with numerous physiological functions, and has been and is at the forefront of both regenerative medicine and cell and tissue engineering (Figure 1). Prevailing techniques to mimic liver functions, like in vitro hepatic tissue engineering, liver cell therapy, organ re-engineering, organ microdevices, and in vivo human-in-mouse livers, have contributed greatly to liver regenerative medicine. However, these techniques depend upon donor hepatocytes and/or livers, or on transgenic mice.

The advent of mouse and human pluripotent stem cells (mPSCs and hPSCs) has led to great strides in using directed differentiation protocols to generate PSC-derived hepatocytes (PSC-Heps). These hPSC-Heps have successfully been used for in vitro liver disease modeling, and mPSC-Heps and hPSC-Heps have reversed injury in mouse liver injury models. Unfortunately, hPSC-Heps demonstrate several signs of being functionally immature in vitro, and as a sign of their immaturity, exhibit greatly limited in vivo liver repopulation. 

New tools or techniques will likely further the development of stem cells and regenerative medicine, as applied to the liver. Multimodality molecular imaging is a rapidly emerging branch of medical imaging, based in biology, chemistry, physics, medical basic sciences, and engineering. In molecular imaging, molecular biological /biochemical processes, such as gene expression, receptor upregulation, and metabolism, are assessed noninvasively and quantitatively in the intact living subject (Figure 2). Molecular imaging is thus directly applicable to understanding stem cell functions in vitro and in vivo, as well as to developing techniques for therapeutic monitoring, molecular diagnostics, and early detection of disease.

The overall objective of our research is to address limitations of existing approaches by combining principles in chemical, biological and biomedical engineering, molecular imaging, and stem cell/developmental biology to develop functioning liver cells/ tissue and to develop new molecular diagnostics and therapeutics for liver diseases.