A Preclinical Model of Human Liver Using Precision Cut Tissue Slice Culture.

Area of Science:

• Biomedical research
• Preclinical drug development
• Tissue engineering

Background:

• Preclinical models like 2D cultures and animal models have limitations in complexity, cost, and human relevance.
• Human precision cut tissue slices (hPCTS) maintain native tissue architecture and microenvironment, bridging the gap between traditional models.
• Novel culture formats are being explored to optimize hPCTS viability and functionality for improved disease modeling.

Purpose of the Study:

• To evaluate and compare the viability and functionality of hPCTS across different culture formats.
• To assess the suitability of a commercially available flow system (CELLBLOKS®) for hPCTS culture.
• To determine the optimal culture method for long-term hPCTS maintenance.

Main Methods:

• hPCTS were cultured for 15 days in three formats: Millicell inserts, CELLBLOKS® flow system, and no insert.
• Cell viability was assessed using MTS assays.
• Tissue functionality was measured by quantifying urea and albumin secretion.

Main Results:

• Millicell inserts demonstrated superior maintenance of hPCTS viability and functionality over 15 days.
• Cultures without inserts showed reduced viability and function after 7 days.
• CELLBLOKS® system resulted in significantly decreased hPCTS viability and function within 3 days.

Conclusions:

• Millicell Biopore™ inserts provide a reliable method for preserving hPCTS viability and function.
• The CELLBLOKS® flow system may be suitable for simpler cell cultures but is less effective for complex hPCTS.
• hPCTS cultured with Millicell inserts represent a promising, human-specific alternative to animal models, supporting the 3Rs in preclinical research.