Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte Viability and Albumin Secretion

• Published in: Journal of Immunology Research Vol. 2018; no. 2018; pp. 1 - 13
• Main Authors: Schuurman, Henk-Jan, Gerber-Lemaire, Sandrine, Gonelle-Gispert, Carmen, Buhler, Leo H., Sidibe, Jonathan, Meyer, Jeremy, Meier, Raphael P. H., Passemard, Solène, Noverraz, François, Szabó, Luca, Pimenta, Joel, Montanari, Elisa, Thomas, Aurelien
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; Hindawi Limited; Wiley
• Subjects: Albumin; Albumins - metabolism; Alginates; Alginic acid; Animals; Antianxiety agents; Atracurium; Catabolism; Cell Survival; Cells, Cultured; Coculture Techniques; Cytokines; Diazepam; Drug Compounding; Glucuronic Acid; Glycols (Class of compounds); Growth factors; Hepatocytes; Hepatocytes - physiology; Hepatocytes - transplantation; Hexuronic Acids; Humans; Hydrogels; Immunology; Legal medicine; Liver; Liver diseases; Liver failure; Liver Failure - therapy; Liver transplantation; Medicine; Mesenchymal stem cells; Mesenchymal Stromal Cells - physiology; Mesenchyme; Metabolism; Microencapsulation; Polyethylene glycol; Rodents; Secretion; Stem cell transplantation; Stem cells; Stromal cells; Swine; Transplantation, Heterologous; Transplants & implants; Viability; United Kingdom
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2018/1078547

Porcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture and coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs (n=9) were harvested, and hepatocytes were isolated from liver suspensions for microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted alginate hydrogels, either alone or in combination with MSC. Viability, albumin secretion, and diazepam catabolism of hepatocytes were measured for one week. 9.2 ± 3.6 × 109 hepatocytes with 95.2 ± 3.1% viability were obtained after isolation. At day 3, free hepatocytes displayed 99% viability, whereas microencapsulation in alginate and PEG-grafted alginate decreased viability to 62% and 48%, respectively. Albumin secretion and diazepam catabolism occurred in free and microencapsulated hepatocytes. Coencapsulation of hepatocytes with MSC significantly improved viability and albumin secretion at days 4 and 8 (p<0.05). Coculture with MSC significantly increased and prolonged albumin secretion. In conclusion, we established a protocol for isolation and microencapsulation of high numbers of viable pig hepatocytes and demonstrated that the presence of MSC is beneficial for the viability and function of porcine hepatocytes.