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Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children.

Identifieur interne : 000274 ( Main/Exploration ); précédent : 000273; suivant : 000275

Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children.

Auteurs : Anil Dhawan [Royaume-Uni] ; Nataruks Chaijitraruch [Thaïlande] ; Emer Fitzpatrick [Royaume-Uni] ; Sanjay Bansal [Royaume-Uni] ; Celine Filippi [Royaume-Uni] ; Sharon C. Lehec [Royaume-Uni] ; Nigel D. Heaton [Royaume-Uni] ; Pauline Kane [Royaume-Uni] ; Anita Verma [Royaume-Uni] ; Robin D. Hughes [Royaume-Uni] ; Ragai R. Mitry [Royaume-Uni]

Source :

RBID : pubmed:31843649

Abstract

BACKGROUND & AIMS

Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis.

METHODS

Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT.

RESULTS

Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions.

CONCLUSION

The results demonstrate the feasibility and safety of an HMB infusion in children with ALF.

LAY SUMMARY

Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.


DOI: 10.1016/j.jhep.2019.12.002
PubMed: 31843649


Affiliations:


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Le document en format XML

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<b>BACKGROUND & AIMS</b>
</p>
<p>Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>METHODS</b>
</p>
<p>Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT.</p>
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<div type="abstract" xml:lang="en">
<p>
<b>RESULTS</b>
</p>
<p>Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>CONCLUSION</b>
</p>
<p>The results demonstrate the feasibility and safety of an HMB infusion in children with ALF.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>LAY SUMMARY</b>
</p>
<p>Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.</p>
</div>
</front>
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<Month>May</Month>
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<Abstract>
<AbstractText Label="BACKGROUND & AIMS" NlmCategory="OBJECTIVE">Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The results demonstrate the feasibility and safety of an HMB infusion in children with ALF.</AbstractText>
<AbstractText Label="LAY SUMMARY" NlmCategory="UNASSIGNED">Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.</AbstractText>
<CopyrightInformation>Copyright © 2019. Published by Elsevier B.V.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Dhawan</LastName>
<ForeName>Anil</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom; Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom. Electronic address: anil.dhawan@kcl.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Chaijitraruch</LastName>
<ForeName>Nataruks</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom; Paediatric Gastroenterology and Hepatology, Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fitzpatrick</LastName>
<ForeName>Emer</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Bansal</LastName>
<ForeName>Sanjay</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Paediatric Liver GI and Nutrition Center, King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Filippi</LastName>
<ForeName>Celine</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lehec</LastName>
<ForeName>Sharon C</ForeName>
<Initials>SC</Initials>
<AffiliationInfo>
<Affiliation>Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Heaton</LastName>
<ForeName>Nigel D</ForeName>
<Initials>ND</Initials>
<AffiliationInfo>
<Affiliation>Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kane</LastName>
<ForeName>Pauline</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Radiology, King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Verma</LastName>
<ForeName>Anita</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Department of Infection Sciences and Microbiology, King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hughes</LastName>
<ForeName>Robin D</ForeName>
<Initials>RD</Initials>
<AffiliationInfo>
<Affiliation>Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Mitry</LastName>
<ForeName>Ragai R</ForeName>
<Initials>RR</Initials>
<AffiliationInfo>
<Affiliation>Dhawan Lab at the Mowat Labs, Institute of Liver Studies, King's College London at King's College Hospital, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2019</Year>
<Month>12</Month>
<Day>13</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>Netherlands</Country>
<MedlineTA>J Hepatol</MedlineTA>
<NlmUniqueID>8503886</NlmUniqueID>
<ISSNLinking>0168-8278</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList>
<CommentsCorrections RefType="CommentIn">
<RefSource>Nat Rev Gastroenterol Hepatol. 2020 Apr;17(4):197-198</RefSource>
<PMID Version="1">32107472</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">Acute liver failure</Keyword>
<Keyword MajorTopicYN="N">Alginate</Keyword>
<Keyword MajorTopicYN="N">Cell transplantation</Keyword>
<Keyword MajorTopicYN="N">Cryopreservation</Keyword>
<Keyword MajorTopicYN="N">Hepatocyte microbeads</Keyword>
<Keyword MajorTopicYN="N">Intraperitoneal transplantation</Keyword>
<Keyword MajorTopicYN="N">Microencapsulated human hepatocytes</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="received">
<Year>2019</Year>
<Month>06</Month>
<Day>17</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised">
<Year>2019</Year>
<Month>12</Month>
<Day>03</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2019</Year>
<Month>12</Month>
<Day>05</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2019</Year>
<Month>12</Month>
<Day>18</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
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<Month>12</Month>
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<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2019</Year>
<Month>12</Month>
<Day>18</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">31843649</ArticleId>
<ArticleId IdType="pii">S0168-8278(19)30714-7</ArticleId>
<ArticleId IdType="doi">10.1016/j.jhep.2019.12.002</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>Royaume-Uni</li>
<li>Thaïlande</li>
</country>
<region>
<li>Angleterre</li>
<li>Grand Londres</li>
</region>
<settlement>
<li>Londres</li>
</settlement>
</list>
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<name sortKey="Bansal, Sanjay" sort="Bansal, Sanjay" uniqKey="Bansal S" first="Sanjay" last="Bansal">Sanjay Bansal</name>
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<name sortKey="Heaton, Nigel D" sort="Heaton, Nigel D" uniqKey="Heaton N" first="Nigel D" last="Heaton">Nigel D. Heaton</name>
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<name sortKey="Kane, Pauline" sort="Kane, Pauline" uniqKey="Kane P" first="Pauline" last="Kane">Pauline Kane</name>
<name sortKey="Lehec, Sharon C" sort="Lehec, Sharon C" uniqKey="Lehec S" first="Sharon C" last="Lehec">Sharon C. Lehec</name>
<name sortKey="Mitry, Ragai R" sort="Mitry, Ragai R" uniqKey="Mitry R" first="Ragai R" last="Mitry">Ragai R. Mitry</name>
<name sortKey="Verma, Anita" sort="Verma, Anita" uniqKey="Verma A" first="Anita" last="Verma">Anita Verma</name>
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