Treating Inborn Errors of Liver Metabolism with Stem Cells: Current Clinical Development

Overview

Journal J Inherit Metab Dis

Publisher Wiley

Date 2014 Mar 27

PMID 24668464

Citations 13

Authors

Etienne Marc Sokal

Affiliations

Soon will be listed here.

Abstract

Advanced therapies including stem cells are currently a major biotechnological development. Adult liver stem cells can differentiate into hepatocyte like cells and be infused in the recipient's liver to bring a missing metabolic function. These cells can be produced in large quantities in vitro. Allogeneic stem cells are required to treat genetic diseases, and this approach allows to use one single source of tissue to treat different diseases and many recipients. Mesenchymal stem cells can in addition play an immunomodulatory and anti-inflammatory role and possibly prevent the accumulation of fibrous tissue in the liver. From a regulatory point of view, stem cells are considered as medicinal products, and must undergo a pharmaceutical development that goes beyond the research and proof-of-concept phases. Here, we review the track followed from the first hepatocyte transplantation in 2000 to the next generation product issued from stem cell technology, and the start of EMA approved clinical trials to evaluate the safety and potency of liver stem cells for the treatment of inborn errors of the liver metabolism.

Citing Articles

Kupffer cells abrogate homing and repopulation of allogeneic hepatic progenitors in injured liver site.

Abbas N, You K, Getachew A, Wu F, Hussain M, Huang X Stem Cell Res Ther. 2024; 15(1):48.

PMID: 38378583 PMC: 10877762. DOI: 10.1186/s13287-024-03656-w.

Hepatic Regeneration in Cirrhosis.

Jindal A, Jagdish R, Kumar A J Clin Exp Hepatol. 2022; 12(2):603-616.

PMID: 35535091 PMC: 9077225. DOI: 10.1016/j.jceh.2021.08.029.

Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice.

Famulari E, Navarro-Tableros V, Herrera Sanchez M, Bortolussi G, Gai M, Conti L Sci Rep. 2020; 10(1):887.

PMID: 31965023 PMC: 6972964. DOI: 10.1038/s41598-020-57820-2.

Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?.

Kholodenko I, Kurbatov L, Kholodenko R, Manukyan G, Yarygin K Cells. 2019; 8(10).

PMID: 31546729 PMC: 6830330. DOI: 10.3390/cells8101127.

Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies.

Coppin L, Najimi M, Bodart J, Rouchon M, Van Der Smissen P, Eeckhoudt S Cells. 2019; 8(8).

PMID: 31394759 PMC: 6721739. DOI: 10.3390/cells8080846.

References

Scheers I, Maerckx C, Khuu D, Marcelle S, Decottignies A, Najimi M . Adult-derived human liver progenitor cells in long-term culture maintain appropriate gatekeeper mechanisms against transformation. Cell Transplant. 2012; 21(10):2241-55. DOI: 10.3727/096368912X639026. View

Donckier V, Lucidi V, Gustot T, Moreno C . Ethical considerations regarding early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapy. J Hepatol. 2013; 60(4):866-71. DOI: 10.1016/j.jhep.2013.11.015. View

Ribes-Koninckx C, Pareja Ibars E, Calzado Agrasot M, Bonora-Centelles A, Polo Miquel B, Vila Carbo J . Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases. Cell Transplant. 2012; 21(10):2267-82. DOI: 10.3727/096368912X637505. View

Stephenne X, Debray F, Smets F, Jazouli N, Sana G, Tondreau T . Hepatocyte transplantation using the domino concept in a child with tetrabiopterin nonresponsive phenylketonuria. Cell Transplant. 2012; 21(12):2765-70. DOI: 10.3727/096368912X653255. View

Fox I, Chowdhury J, Kaufman S, Goertzen T, CHOWDHURY N, Warkentin P . Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. 1998; 338(20):1422-6. DOI: 10.1056/NEJM199805143382004. View

Stephenne X, Najimi M, Smets F, Reding R, de Ville de Goyet J, Sokal E . Cryopreserved liver cell transplantation controls ornithine transcarbamylase deficient patient while awaiting liver transplantation. Am J Transplant. 2005; 5(8):2058-61. DOI: 10.1111/j.1600-6143.2005.00935.x. View

Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I . Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008; 371(9624):1579-86. DOI: 10.1016/S0140-6736(08)60690-X. View

Ambrosino G, Varotto S, Strom S, Guariso G, Franchin E, Miotto D . Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 2005; 14(2-3):151-7. DOI: 10.3727/000000005783983250. View

Sokal E, Smets F, Bourgois A, Van Maldergem L, Buts J, Reding R . Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up. Transplantation. 2003; 76(4):735-8. DOI: 10.1097/01.TP.0000077420.81365.53. View

10.

Perito E, Rhee S, Roberts J, Rosenthal P . Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for 2002-2012. Liver Transpl. 2013; 20(1):89-99. PMC: 3877181. DOI: 10.1002/lt.23765. View

11.

Stephenne X, Najimi M, Sibille C, Nassogne M, Smets F, Sokal E . Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency. Gastroenterology. 2006; 130(4):1317-23. DOI: 10.1053/j.gastro.2006.01.008. View

12.

Harding C, Gibson K . Therapeutic liver repopulation for phenylketonuria. J Inherit Metab Dis. 2010; 33(6):681-7. DOI: 10.1007/s10545-010-9099-1. View

13.

Najimi M, Khuu D, Lysy P, Jazouli N, Abarca J, Sempoux C . Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes?. Cell Transplant. 2007; 16(7):717-28. DOI: 10.3727/000000007783465154. View

14.

Remberger M, Mattsson J, Hassan Z, Karlsson N, LeBlanc K, Omazic B . Risk factors for acute graft-versus-host disease grades II-IV after reduced intensity conditioning allogeneic stem cell transplantation with unrelated donors: a single centre study. Bone Marrow Transplant. 2007; 41(4):399-405. DOI: 10.1038/sj.bmt.1705913. View

15.

Dhawan A, Mitry R, Hughes R, Lehec S, Terry C, Bansal S . Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. 2004; 78(12):1812-4. DOI: 10.1097/01.tp.0000146386.77076.47. View

16.

Pareja E, Ribes C, Gomez-Lechon M, Cortes M, Vila J, Dalmau J . [Liver cell therapy in the treatment of inborn errors of metabolism in children]. An Pediatr (Barc). 2013; 79(6):390.e1-8. DOI: 10.1016/j.anpedi.2013.05.018. View

17.

Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F . An estimation of the number of cells in the human body. Ann Hum Biol. 2013; 40(6):463-71. DOI: 10.3109/03014460.2013.807878. View

18.

Ban K, Sugiyama N, Sugiyama K, Wada Y, Suzuki T, Hashimoto T . A pediatric patient with classical citrullinemia who underwent living-related partial liver transplantation. Transplantation. 2001; 71(10):1495-7. DOI: 10.1097/00007890-200105270-00026. View

19.

Muraca M, Gerunda G, Neri D, Granato A, Feltracco P, Meroni M . Hepatocyte transplantation as a treatment for glycogen storage disease type 1a. Lancet. 2002; 359(9303):317-8. DOI: 10.1016/S0140-6736(02)07529-3. View

20.

Andries S, Casamayou L, Sempoux C, Burlet M, Reding R, Bernard Otte J . Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine. Transplantation. 2001; 72(2):267-72. DOI: 10.1097/00007890-200107270-00018. View