A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors
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 t...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55217-7 |
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| author | Umberto Cillo Caterina Lonati Alessandra Bertacco Lucrezia Magnini Michele Battistin Liver NMP Consortium Lara Borsetto Francesco Dazzi David Al-Adra Enrico Gringeri Maria Laura Bacci Andrea Schlegel Daniele Dondossola |
| author_facet | Umberto Cillo Caterina Lonati Alessandra Bertacco Lucrezia Magnini Michele Battistin Liver NMP Consortium Lara Borsetto Francesco Dazzi David Al-Adra Enrico Gringeri Maria Laura Bacci Andrea Schlegel Daniele Dondossola |
| author_sort | Umberto Cillo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4f06d0f4c0a6411ca0c0f3a26ebd018f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4f06d0f4c0a6411ca0c0f3a26ebd018f2025-01-05T12:40:24ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-024-55217-7A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactorsUmberto Cillo0Caterina Lonati1Alessandra Bertacco2Lucrezia Magnini3Michele Battistin4Liver NMP ConsortiumLara Borsetto5Francesco Dazzi6David Al-Adra7Enrico Gringeri8Maria Laura Bacci9Andrea Schlegel10Daniele Dondossola11Hepato-Biliary-Pancreatic Surgery and Liver Transplant Unit, General Surgery 2, Department of Surgical, Oncological and Gastroenterological Sciences, University of PaduaCenter for Preclinical Research, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9Hepato-Biliary-Pancreatic Surgery and Liver Transplant Unit, General Surgery 2, Department of Surgical, Oncological and Gastroenterological Sciences, University of PaduaCenter for Preclinical Research, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9Center for Preclinical Research, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9Hepato-Biliary-Pancreatic Surgery and Liver Transplant Unit, General Surgery 2, Department of Surgical, Oncological and Gastroenterological Sciences, University of PaduaSchool of Cardiovascular and Metabolic Medicine & Sciences, King’s College LondonDivision of Transplantation, Department of Surgery, School of Medicine and Public Health, University of WisconsinHepato-Biliary-Pancreatic Surgery and Liver Transplant Unit, General Surgery 2, Department of Surgical, Oncological and Gastroenterological Sciences, University of PaduaDepartment of Veterinary Medical Sciences, University of BolognaCenter for Preclinical Research, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35Abstract 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.https://doi.org/10.1038/s41467-024-55217-7 |
| spellingShingle | Umberto Cillo Caterina Lonati Alessandra Bertacco Lucrezia Magnini Michele Battistin Liver NMP Consortium Lara Borsetto Francesco Dazzi David Al-Adra Enrico Gringeri Maria Laura Bacci Andrea Schlegel Daniele Dondossola A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors Nature Communications |
| title | A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| title_full | A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| title_fullStr | A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| title_full_unstemmed | A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| title_short | A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| title_sort | proof of concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors |
| url | https://doi.org/10.1038/s41467-024-55217-7 |
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