A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors

Umberto Cillo, Caterina Lonati (), Alessandra Bertacco, Lucrezia Magnini, Michele Battistin, Lara Borsetto, Francesco Dazzi, David Al-Adra, Enrico Gringeri, Maria Laura Bacci, Andrea Schlegel and Daniele Dondossola
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Umberto Cillo: University of Padua
Caterina Lonati: Via Pace 9
Alessandra Bertacco: University of Padua
Lucrezia Magnini: Via Pace 9
Michele Battistin: Via Pace 9
Lara Borsetto: University of Padua
Francesco Dazzi: King’s College London
David Al-Adra: School of Medicine and Public Health, University of Wisconsin
Enrico Gringeri: University of Padua
Maria Laura Bacci: University of Bologna
Andrea Schlegel: Via Pace 9
Daniele Dondossola: Via Francesco Sforza 35

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55217-7

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