A Proof-of-concept Study in Small and Large Animal Models for Coupling Liver Normothermic Machine Perfusion with Mesenchymal Stromal Cell Bioreactors

Overview

Journal Nat Commun

Specialty Biology

Date 2025 Jan 2

PMID 39746966

Authors

Umberto Cillo

Caterina Lonati

Alessandra Bertacco

Lucrezia Magnini

Michele Battistin

Lara Borsetto

Francesco Dazzi

David Al-Adra

Enrico Gringeri

Maria Laura Bacci

Andrea Schlegel

Daniele Dondossola

Affiliations

Soon will be listed here.

Abstract

To fully harness mesenchymal-stromal-cells (MSCs)' benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP. Liver NMP induced specific, liver-tailored, changes in MSCs' secretome. Rat livers exposed to bioreactor-based perfusion produced more bile, released less damage and pro-inflammatory biomarkers, and showed improved mithocondrial function than those subjected to standard NMP. MSC-bioreactor integration into a clinical device resulted in no machine failure and perfusion-related injury. This proof-of-concept study presents a novel MSC-based liver NMP platform that could reduce the deleterious effects of ischemia/reperfusion before transplantation.

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