Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency |
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Authors: | Stéphenne Xavier Najimi Mustapha Sibille Catherine Nassogne Marie-Cécile Smets Françoise Sokal Etienne M |
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Affiliation: | Laboratoire d'hépatologie Pédiatrique et Transplantation Cellulaire, Département GYPE, Service de Pédiatrie, Université Catholique de Louvain & Cliniques St Luc, Brussels, Belgium. |
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Abstract: | BACKGROUND & AIMS: Donor cell engraftment with expression of enzyme activity is the goal of liver cell transplantation for inborn errors of liver metabolism with a view to achieving sustained metabolic control. METHODS: Sequential hepatic cell transplantations using male and female cells were performed in a 3.5-year-old girl with argininosuccinate lyase deficiency over a period of 5 months. Beside clinical, psychomotor, and metabolic follow-up, engraftment was analyzed in repeated liver biopsies (2.5, 5, 8, and 12 months after first infusion) by fluorescence in situ hybridization for the Y-chromosome and by measurement of tissue enzyme activity. RESULTS: Metabolic control was achieved together with psychomotor catch-up, changing the clinical phenotype from a severe neonatal one to a moderate late-onset type. The child was no longer hospitalized and was able to attend normal school. Sustained engraftment of male donor liver cells was shown in repeated biopsies, reaching 19% at 8 months and 12.5% at the 12-month follow-up. XXYY tetraploid donor cells were mainly detected during the infusion period (2.5- and 5-month biopsies), whereas in the follow-up 8-month and 1-year biopsies, diploid donor cell subpopulations had become dominant. Moreover, argininosuccinate lyase activity, originally absent, became measurable in 2 different biopsy samples at 8 months, reaching 3% of control activity, indicating in situ metabolic effect and supporting the clinical evolution to a moderate form of the disease. CONCLUSIONS: Liver cell transplantation can achieve donor cell engraftment in humans in a significant proportion, leading to sustained metabolic and clinical control with psychomotor catch-up. |
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Keywords: | ASA argininosuccinic acid ASL argininosuccinate lyase CK-7 cytokeratin-7 FISH fluorescence in situ hybridization LCT liver cell transplantation OLT orthotopic liver transplantation |
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