A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip Platforms

Area of Science:

• Oncology
• Hepatology
• Biomedical Engineering

Background:

• Metastasis is the primary cause of cancer mortality, with the liver being a common site for solid tumor spread.
• Current animal models fail to replicate human liver heterogeneity and drug metabolism, hindering effective cancer drug development.
• Accurate human liver models are essential for studying liver metastases and developing personalized medicine.

Purpose of the Study:

• To review the development and application of an all-human 3D ex vivo hepatic microphysiological system (MPS) for investigating human liver micrometastases.
• To discuss the sources of liver resident cells, particularly induced pluripotent stem cell (iPSC)-derived hepatocytes, for these models.
• To examine the challenges and limitations in accurately modeling the human liver for disease and drug studies.

Main Methods:

• Adaptation of an all-human 3D ex vivo hepatic microphysiological system (liver-on-a-chip).
• Focus on utilizing iPSC-derived hepatocytes and other liver resident cells.
• Review of existing literature on cell sources, challenges, and limitations in liver modeling.

Main Results:

• The review highlights the potential of liver-on-a-chip technology to model human liver micrometastases.
• It examines the advantages and disadvantages of various cell sources, including iPSC-derived hepatocytes.
• Identifies key challenges in creating accurate and predictive human liver models.

Conclusions:

• All-human liver-on-a-chip models offer a promising platform for studying liver metastases and improving drug discovery.
• Understanding cell source variability and addressing modeling limitations are critical for advancing personalized medicine.
• Further research is needed to optimize these models for clinical relevance.