Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocytes Viability and Albumin Secretion.
1Department of Surgery, University of Geneva, Geneva, Switzerland
2University Centre of Legal Medicine, Universities of Lausanne and Geneva, Geneva and Lausanne, Switzerland
3Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Meeting: 2017 American Transplant Congress
Abstract number: D16
Keywords: Hepatocytes, Pig, Xenotransplantation
Session Information
Session Name: Poster Session D: Cellular & Bone Marrow Transplantation Session II
Session Type: Poster Session
Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Aim: Acute liver failure carries a very high mortality and transplantation of encapsulated pig hepatocytes might temporarily compensate the metabolic functions until the dysfunctional liver recovers its capacity. To advance cell xenotransplantation techniques to clinical application, we standardized the isolation process of high number of viable pig hepatocytes and we tested the effect of co-encapsulation with human bone marrow-derived Mesenchymal Stromal Cells (MSC) on viability and functionality of encapsulated pig hepatocytes.
Methods:Livers from 10kg pigs (n=10) were harvested and perfused ex vivo through the portal vein with a collagenase solution. Hepatocytes were then isolated from the liver suspension by low-speed centrifugation and cells were encapsulated using alginate and poly(ethylene glycol) (PEG)-grafted alginate polymeric hydrogels, either alone or in combination with human MSC. Viability (FDA-PI), albumin secretion, Lidocaine and Diazepam catabolism were measured during one week. Morphology of pellet-cultured hepatocytes with MSC was analyzed by immunofluorescence at day 3.
Results:A total of 9.89±3.6 x109 hepatocytes with 95.65±2.96 % viability were obtained after cell isolation. At day 3, free hepatocytes displayed 99% viability, whereas alginate and PEG-grafted alginate encapsulated hepatocytes showed 50% and 30% viability, respectively. Albumin secretion, Lidocaine and Diazepam catabolism was maintained in free and encapsulated hepatocytes for one week. MSC co-transplantation significantly improved viability and albumin secretion at day 3 and 4 (p<0.05). MSC and hepatocyte formed heterogeneous cell clusters where vimentin-positive MSC were intermingled to albumin-positive porcine hepatocytes.
Conclusions: We developed a standardized protocol to isolate high numbers of viable pig hepatocytes, an important step towards xenotransplantation in humans. Co-culture of pig hepatocytes with human MSC resulted in increased viability and albumin secretion, demonstrating the beneficial effect of human MSC on porcine hepatocytes.
CITATION INFORMATION: Montanari E, Pimenta J, Schuurman H.-J, Meier J, Meyer R, Balaphas A, Sidibé J, Thomas A, Passemard S, Gerber-Lemaire S, Gonelle-Gispert C, Buhler L. Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocytes Viability and Albumin Secretion. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Montanari E, Pimenta J, Schuurman H-J, Meier J, Meyer R, Balaphas A, Sidibé J, Thomas A, Passemard S, Gerber-Lemaire S, Gonelle-Gispert C, Buhler L. Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocytes Viability and Albumin Secretion. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/beneficial-effects-of-human-mesenchymal-stromal-cells-on-porcine-hepatocytes-viability-and-albumin-secretion/. Accessed May 25, 2025.« Back to 2017 American Transplant Congress