Tissue-Engineered Hepatocyte Sheets Supplemented with Adipose-Derived Stem Cells.

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Hepatology

Background:

• Hepatocyte transplantation is a bridge therapy for liver failure but suffers from low and transient effectiveness.
• Engineering functional liver tissue requires long-term maintenance of hepatocyte viability and function.
• Adipose-derived stem cells (ADSCs) have immunomodulatory and trophic properties that may support hepatocyte function.

Purpose of the Study:

• To evaluate the effect of ADSCs on hepatocyte viability, function, and subcutaneous engraftment.
• To assess the potential of hepatocyte-ADSC composite sheets for liver tissue engineering.
• To investigate the underlying mechanisms of ADSC-mediated support for hepatocytes.

Main Methods:

• Hepatocyte-ADSC composite sheets were fabricated using temperature-responsive culture dishes.
• In vitro assays assessed hepatocyte viability and albumin secretion.
• Subcutaneous transplantation in immunodeficient mice evaluated engraftment and hepatocyte survival.
• Cytokine analysis and immunohistochemistry identified molecular signaling pathways.

Main Results:

• Hepatocyte viability was significantly sustained in hepatocyte-ADSC composite sheets compared to hepatocyte-only sheets.
• Albumin secretion was markedly higher in the composite sheets (70.5 μg/mL) versus hepatocyte-only sheets (24.0 μg/mL).
• ADSCs secreted hepatocyte growth factor and interleukin-6, enhancing hepatocyte signaling pathways (p-STAT3, c-MET) and improving engraftment without vascular preconditioning.

Conclusions:

• Hepatocyte-ADSC composite sheets enhance hepatocyte viability and function through paracrine signaling from ADSCs.
• These composite sheets demonstrate improved subcutaneous engraftment, offering a more effective strategy for liver tissue engineering.
• This approach presents a promising, less invasive alternative to traditional hepatocyte transplantation.