Abstract
The applications, outcomes and future strategies of hepatocyte transplantation (HTx) as a corrective intervention for inherited metabolic disease (IMD) are described. An overview of HTx in IMDs, as well as preclinical evaluations in rodent and other mammalian models, is summarized. Current treatments for IMDs are highlighted, along with short- and long-term outcomes and the potential for HTx to supplement or supplant these treatments. Finally, the advantages and disadvantages of HTx are presented, highlighted by long-term challenges with interorgan engraftment and expansion of transplanted cells, in addition to the future prospects of stem cell transplants. At present, the utility of HTx is represented by the potential to bridge patients with life-threatening liver disease to organ transplantation, especially as an adjuvant intervention where severe organ shortages continue to pose challenges.
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Abbreviations
- AGT:
-
Alanine glyoxylate transaminase
- APOLT:
-
Auxiliary partial orthotopic liver transplant
- ASL:
-
Argininosuccinate lyase
- ASS:
-
Argininosuccinate synthetase
- BCAA:
-
Branched-chain amino acids
- BCKA:
-
Branched-chain keto acids
- BCKDH:
-
Branched-chain ketoacid dehydrogenase complex
- CNSI:
-
Crigler-Najjar syndrome type I
- CPSI:
-
Carbamoyl phosphate synthetase I
- FAH:
-
Fumarylacetoacetate hydrolase deficiency (tyrosinemia type I)
- GSD:
-
Glycogen storage disease
- GI:
-
Gastrointestinal
- HDL:
-
High density lipoprotein
- HGF:
-
Hepatic growth factor
- HTx:
-
Hepatocyte transplantation
- KIC:
-
α-Ketoisocaproic acid
- LDL:
-
Low density lipoprotein
- MSUD:
-
Maple syrup urine disease
- NAGS:
-
N-acetylglutamate synthetase
- OLT:
-
Orthotopic liver transplantation
- OTC:
-
Ornithine transcarbamylase
- PFIC:
-
Progressive familial intrahepatic cholestasis
- PHE:
-
Phenylalanine
- PH:
-
Primary Hyperoxaluria
- PKU:
-
Phenylketonuria
- UGT:
-
Bilirubin-UDP-glucuronosyl transferase
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Communicated by: Jerry Vockley
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Vogel, K.R., Kennedy, A.A., Whitehouse, L.A. et al. Therapeutic hepatocyte transplant for inherited metabolic disorders: functional considerations, recent outcomes and future prospects. J Inherit Metab Dis 37, 165–176 (2014). https://doi.org/10.1007/s10545-013-9656-5
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DOI: https://doi.org/10.1007/s10545-013-9656-5