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<p>To fully harness mesenchymal-stromal-cells (MSCs)’ benefits during Normothermic&#xa0;Machine&#xa0;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&#xa0;packages: 1) Development (<i>n</i> = 5): MSC-bioreactors were subjected to 4&#xa0;h-liverless perfusion; 2) Rat model (<i>n</i> = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (<i>n</i> = 6): livers were perfused using a clinical device integrated with a&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月2日

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  • Umberto Cillo,
  • Caterina Lonati,
  • Alessandra Bertacco,
  • Lucrezia Magnini,
  • Michele Battistin,
  • Domenico Ventrella,
  • Camilla Aniballi,
  • Margherita Carbonaro,
  • Andrea Carlin,
  • Alberto Elmi,
  • Lara Borsetto,
  • Francesco Dazzi,
  • David Al-Adra,
  • Enrico Gringeri,
  • Maria Laura Bacci,
  • Andrea Schlegel,
  • Daniele Dondossola

摘要

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.