First Application of a Mixed Porcine-Human Repopulated Bioengineered Liver in a Preclinical Model of Post-Resection Liver Failure.

Autor:	Felgendreff P; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA.; Department of General, Visceral and Transplantation Surgery, Hannover Medical School, 30625 Hannover, Germany., Hosseiniasl SM; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA., Minshew A; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA., Amiot BP; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA., Wilken S; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA., Ahmadzada B; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA., Huebert RC; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA., Sakrikar NJ; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA., Engles NG; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA., Halsten P; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Mariakis K; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Barry J; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Riesgraf S; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Fecteau C; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Ross JJ; Miromatrix Medical Inc., Eden Prairie, MN 55344, USA., Nyberg SL; Department of Surgery, Mayo Clinic, Rochester, MN 55902, USA.; William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN 55902, USA.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2024 Jun 07; Vol. 12 (6). Date of Electronic Publication: 2024 Jun 07.
DOI:	10.3390/biomedicines12061272
Abstrakt:	In this study, a mixed porcine-human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL). PRLF was induced by performing an 85% liver resection in domestic white pigs and randomized into the following three groups 24 h after resection: standard medical therapy (SMT) alone, SMT + extracorporeal circuit (ECC), and SMT + MPH-BEL. The detoxification and metabolic functions of the MPH-BEL grafts were compared to FH-BEL grafts which were perfused in vitro. During the 24 h treatment interval, INR values normalized within 18 h in the MPH-BEL therapy group and urea synthesis increased as compared to the SMT and SMT + ECC control groups. The MPH-BEL treatment was associated with more rapid decline in hematocrit and platelet count compared to both control groups. Histological analysis demonstrated platelet sequestration in the MPH-BEL grafts, possibly related to immune activation. Significantly higher rates of ammonia clearance and metabolic function were observed in the FH-BEL grafts perfused in vitro than in the MPH-BEL grafts. The MPH-BEL treatment was associated with improved markers of liver function in PRLF. Further improvement in liver function in the BEL grafts was observed by seeding the biomatrix with human hepatocytes. Methods to reduce platelet sequestration within BEL grafts is an area of ongoing research.
Databáze:	MEDLINE
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