Abstract
A 3-year-old girl suffering from ornithine carbamoyltransferase (OTC) deficiency was poorly equilibrated under conventional diet and scavenger treatment. Following unsuccessful cryopreserved hepatocyte transplantation, she received two infusions of Adult Derived Human Liver Stem/Progenitor Cells (ADHLSCs) expanded in vitro under GMP settings, the quantity being equivalent to 0.75% of her calculated liver mass. Using FISH immunostaining for the Y chromosome, the initial biopsy did not detect any male nuclei in the recipient liver. Two liver biopsies taken 100 days after ADHLSC transplantation showed 3% and 5% of male donor cells in the recipient liver, thus suggesting repopulation by donor cells. Although limited follow-up did not allow us to draw conclusions on long-term improvement, these results provide a promising proof of concept that this therapy is feasible in an OTC patient.
Competing interests: None declared
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Communicated by: Daniela Karall
Appendices
Take-Home Message
Liver stem cells infused in the portal vein engraft and repopulate the liver in an OTC patient.
Compliance with Guidelines
This cell transplantation protocol was approved by the ethical committee of the institution and informed consent was given to and received from the parents by an independent physician.
Conflict of Interest
Etienne Sokal declares to own patent rights on ADHLSC, currently in clinical development plan (clinicaltrial.gov identifier NCT01765283) by Promethera Biosciences, spinoff of the laboratory of pediatric hepatology and cell therapy. ES Sokal is consultant CSO for Promethera Biosciences.
Xavier Stephenne declares that he has no conflict of interest.
Chris Ottolenghi declares no conflict of interest.
Nawal Jazouli declares no conflict of interest.
Florence Lacaille declares no conflict of interest.
Mustapha Najimi declares to own patent rights on ADHLSC, currently in clinical development (clinicaltrial.gov identifier NCT01765283). MN is consultant for Promethera Biosciences.
Pascale de Lonlay declares no conflict of interest.
Françoise Smets declares that she is currently principal investigator of a clinical trial (clinicaltrial.gov identifier NCT01765283).
Animal Rights: All preclinical animal studies done prior to the reported work were approved by the Institution Animal Ethical Committee.
Informed consent of the patient was obtained from her legal representative, and the protocol and informed consent was approved by the Université Catholique de Louvain & Cliniques St Luc Ethical committee. An ethical committee independent delegate explained the study to the patient and her legal representative.
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Sokal, E.M. et al. (2013). Liver Engraftment and Repopulation by In Vitro Expanded Adult Derived Human Liver Stem Cells in a Child with Ornithine Carbamoyltransferase Deficiency. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_257
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DOI: https://doi.org/10.1007/8904_2013_257
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