Hepatocyte Transplantation Transforms Severe Phenylketonuria to Mild Hyperphenylalaninemia

Smets, Françoise; Stéphenne, Xavier; Debray, Guillaume; Menten, Renaud; Reding, Raymond; Najimi, Mustapha; Sokal, Étienne

doi:10.1016/s0016-5085(11)64003-1

Cited by 5 publications

(2 citation statements)

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“…Hepatocytes for the first infusion were isolated from an explanted liver from a 14‐month‐old girl with GSD‐Ib undergoing liver transplantation. After the second transplantation with cells from a normal donor, phenylalanine levels decreased by 70%, and the half‐life of phenylalanine decreased from 41.6 to 19.1 h .…”

Section: Indications For Hepatocyte Transplantation: Preclinical Modementioning

confidence: 99%

“…Of interest, it was recently suggested that explanted livers from patients with metabolic liver diseases undergoing liver transplantation could provide a new source of hepatocytes for the so‐called domino hepatocyte transplantation (Gramignoli et al . Submitted) . Domino liver transplantation has been used successfully to increase the donor pool .…”

Section: Cell Sourcesmentioning

confidence: 99%

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Hepatocyte transplantation for inherited metabolic diseases of the liver

et al. 2012

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Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation.Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

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Section: Indications For Hepatocyte Transplantation: Preclinical Modementioning

confidence: 99%

Section: Cell Sourcesmentioning

confidence: 99%

Hepatocyte transplantation for inherited metabolic diseases of the liver

et al. 2012

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Concise Review: Cell Therapies for Hereditary Metabolic Liver Diseases—Concepts, Clinical Results, and Future Developments

2015

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The concept of cell-based therapies for inherited metabolic liver diseases has been introduced for now more than 40 years in animal experiments, but controlled clinical data in humans are still not available. In the era of dynamic developments in stem cell science, the "right" cell for transplantation is considered as an important key for successful treatment. Do we aim to transplant mature hepatocytes or do we consider the liver as a stem/progenitor-driven organ and replenish the diseased liver with genetically normal stem/progenitor cells? Although conflicting results from cell tracing and transplantation experiments have recently emerged about the existence and role of stem/progenitor cells in the liver, their overall contribution to parenchymal cell homeostasis and tissue repair is limited. Accordingly, engraftment and repopulation efficacies of extrahepatic and liver-derived stem/progenitor cell types are considered to be lower compared to mature hepatocytes. On the basis of these results, we will discuss the current clinical cell transplantation programs for inherited metabolic liver diseases and future developments in liver cell therapy. STEM CELLS 2015;33:1055-1062 HEPATOCYTES OR STEM CELLS: WHICH CELL DRIVES PARENCHYMAL LIVER MAINTENANCE AND REGENERATION OF THE LIVER?The long prevailing view in liver physiology and pathophysiology has localized a hepatic stem/progenitor cell compartment at or near the canals of Hering, in periductular glands and in extrahepatic bile duct structures [1][2][3]. Some researchers found proof that biliary tree-associated stem/progenitor cells countinuously generate hepatocytes and bile duct cells and maintain the normal turnover of parenchymal liver cells [4]. According to the "streaming theory," stem/progenitor cellderived hepatocytes continuously migrate from the periportal areas toward central vein structures, mature and express differential metabolic activities. Cell fate tracing experiments have attributed Sox9 expressing cells with stem/progenitor properties in the liver as well as in several other epithelial organs [5][6][7]. More recent data challenge this view and provide evidence for a more complex situation in the liver.Following acute injury small cells, which express the WNT ligand receptor Lgr5, emerge in the liver and generate hepatocytes [8]. These cells were identified randomly throughout the liver and could not be traced in the noninjured liver. Although the Lgr5 1 cells, which coexpress Krt19 and Sox9, could still be derived from a (not identified) biliary lineagederived stem/progenitor cell in the liver, other studies indicate that mature hepatocytes can dedifferentiate and acquire properties of a liver stem/progenitor cell including the expression of progenitor and biliary lineageassociated cell surface markers. "Knockdown" of the Hippo/Yes-associated protein (YAP) signalling pathway in hepatocytes resulted in emergence of cells with liver stem/progenitor characteristics. Upon restauration of YAP expression, at least some progenitor cells turned ...

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Liver cell therapies: cellular sources and grafting strategies

Zhang

Cui

et al. 2023

Front. Med.

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Hepatocyte Transplantation Transforms Severe Phenylketonuria to Mild Hyperphenylalaninemia

Cited by 5 publications

References 0 publications

Hepatocyte transplantation for inherited metabolic diseases of the liver

Hepatocyte transplantation for inherited metabolic diseases of the liver

Concise Review: Cell Therapies for Hereditary Metabolic Liver Diseases—Concepts, Clinical Results, and Future Developments

Liver cell therapies: cellular sources and grafting strategies

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