Anil Dhawan1, Nataruks Chaijitraruch2, Emer Fitzpatrick3, Sanjay Bansal3, Celine Filippi4, Sharon C Lehec4, Nigel D Heaton5, Pauline Kane6, Anita Verma7, Robin D Hughes4, Ragai R Mitry4. 1. Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom; Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom. Electronic address: anil.dhawan@kcl.ac.uk. 2. Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom; Paediatric Gastroenterology and Hepatology, Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom. 4. Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom. 5. Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, United Kingdom. 6. Department of Radiology, King's College Hospital, London, United Kingdom. 7. Department of Infection Sciences and Microbiology, King's College Hospital, London, United Kingdom.
Abstract
BACKGROUND & AIMS: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. METHODS: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. RESULTS: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. LAY SUMMARY: Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.
BACKGROUND & AIMS: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. METHODS: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. RESULTS: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. LAY SUMMARY:Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.
Authors: Rute A Tomaz; Ekaterini D Zacharis; Fabian Bachinger; Annabelle Wurmser; Daniel Yamamoto; Sandra Petrus-Reurer; Carola M Morell; Dominika Dziedzicka; Brandon T Wesley; Imbisaat Geti; Charis-Patricia Segeritz; Miguel C de Brito; Mariya Chhatriwala; Daniel Ortmann; Kourosh Saeb-Parsy; Ludovic Vallier Journal: Elife Date: 2022-08-12 Impact factor: 8.713
Authors: Adam M Syanda; Vera I Kringstad; Samuel J I Blackford; Joachim S Kjesbu; Soon Seng Ng; Liang Ma; Fang Xiao; Abba E Coron; Anne Mari A Rokstad; Sunil Modi; S Tamir Rashid; Berit Løkensgard Strand Journal: Front Bioeng Biotechnol Date: 2022-03-03