Protection of liver sinusoidal endothelial cells using different preservation solutions

Area of Science:

• Transplantation Immunology
• Cell Biology
• Organ Preservation

Background:

• Liver sinusoidal endothelial cell (LSEC) integrity is vital for liver transplant success.
• Optimizing preservation solutions is key to maintaining LSEC barrier function.

Purpose of the Study:

• To evaluate the efficacy of different preservation solutions in maintaining LSEC barrier function and integrity.
• To compare University of Wisconsin machine perfusion solution (UW-MPS) with histidine-tryptophan-ketoglutarate and endothelial cell growth medium 2 (EGM2).

Main Methods:

• Incubation of LSECs and human umbilical vein endothelial cells (HUVECs) in UW-MPS, histidine-tryptophan-ketoglutarate, or EGM2.
• Assessment of endothelial integrity via morphology, membrane protein expression (PECAM-1, ICAM-1, CD32b), and electric cell-substrate impedance sensing.
• Evaluation of response to tumor necrosis factor-alpha (TNF-α) using trans-endothelial migration (TEM) assays.

Main Results:

• EGM2 promoted barrier function and monolayer recovery in LSECs and HUVECs.
• UW-MPS reduced PECAM-1 expression and significantly inhibited neutrophil adhesion and TEM under inflammatory conditions.
• All solutions maintained high PECAM-1 expression, while ICAM-1 increased with TNF-α stimulation.

Conclusions:

• Endothelial cell growth medium 2 (EGM2) demonstrates superior preservation of endothelial barrier function compared to UW-MPS.
• Optimized preservation solutions like EGM2 are critical for maintaining endothelial integrity, potentially improving liver transplantation outcomes.