The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Isolated Hepatocyte Transplantation in an Infant With a Severe Urea Cycle Disorder
Abstract
Objective. Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency. Methods. An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids. Results. Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age. Conclusions. Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.
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“Hepatocyte cell therapy is an attractive alternative to liver transplantation1, 2.”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [2]
Citations
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Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M.-L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., et al. (2010) · Nature Medicine · doi:10.1038/nm.2170 · Cited by 1,370
Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision
Häberle, J., Burlina, A., Chakrapani, A., Dixon, M., Karall, D., Lindner, M. S., Mandel, H., Martinelli, D., Pintos‐Morell, G., Santer, R., et al. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12100 · Cited by 510
Hepatic progenitor cells of biliary origin with liver repopulation capacity
Lu, W.-Y., Bird, T. G., Boulter, L., Tsuchiya, A., Cole, A. M., Hay, T., Guest, R. V., Wojtacha, D., Man, T. Y., Mackinnon, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3203 · Cited by 479
Human Hepatocyte Transplantation: Worldwide Results
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Self-citationDecellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation
Mazza, G., Rombouts, K., Rennie Hall, A., Urbani, L., Vinh Luong, T., Al-Akkad, W., Longato, L., Brown, D., Maghsoudlou, P., Dhillon, A. P., et al. (2015) · Scientific Reports · doi:10.1038/srep13079 · Cited by 415
Metadata
- Authors
- Horslen, S. P., McCowan, T. C., Goertzen, T. C., Warkentin, P. I., Cai, H. B., Strom, S. C., & Fox, I. J.
- Affiliations
- University of Nebraska Medical Center (US)
- University of Pittsburgh Medical Center (US)
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2003-06-01
- Volume
- 111
- Issue
- 6
- Pages
- 1262-1267
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- OpenAlex
- W2058848231
- Cited by
- 295
- References
- 16
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 12 · 2015: 17 · 2014: 10 · 2013: 22 · 2012: 22
- FWCI
- 12.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PEDIATRICS (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- ornithine transcarbamylase deficiency, urea cycle disorders, hyperammonemia, inborn errors of metabolism, immunosuppression, tacrolimus, collagenase perfusion, liver transplantation, protein intolerance, 4-phenylbutyric acid
- MeSH terms
- Adult, Crigler-Najjar Syndrome, Female, Genetic Carrier Screening, Humans, Infant, Male, Prenatal Diagnosis, Urea, Liver Transplantation, Ornithine Carbamoyltransferase Deficiency Disease, Hyperammonemia, Hepatocytes
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