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Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production
A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581169/ https://www.ncbi.nlm.nih.gov/pubmed/34678209 http://dx.doi.org/10.1016/j.stemcr.2021.09.018 |
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author | Larson, Ellen L. Joo, Dong Jin Nelson, Erek D. Amiot, Bruce P. Aravalli, Rajagopal N. Nyberg, Scott L. |
author_facet | Larson, Ellen L. Joo, Dong Jin Nelson, Erek D. Amiot, Bruce P. Aravalli, Rajagopal N. Nyberg, Scott L. |
author_sort | Larson, Ellen L. |
collection | PubMed |
description | A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mutations in the recipient embryo to disable hepatogenesis, and discuss the advantages of using fumarylacetoacetate hydrolase knockouts and other genetic modifications to disable hepatogenesis. Interspecies blastocyst complementation using porcine recipients for primate donors has been achieved, although percentages of chimerism remain persistently low. Recent investigation into the dynamic transcriptomes of pigs and primates have created new opportunities to intimately match the stage of developing animal embryos with one of the many varieties of human induced pluripotent stem cell. We discuss techniques for decreasing donor cell apoptosis, targeting donor tissue to endodermal structures to avoid neural or germline chimerism, and decreasing the immunogenicity of chimeric organs by generating donor endothelium. |
format | Online Article Text |
id | pubmed-8581169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85811692021-11-18 Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production Larson, Ellen L. Joo, Dong Jin Nelson, Erek D. Amiot, Bruce P. Aravalli, Rajagopal N. Nyberg, Scott L. Stem Cell Reports Perspective A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mutations in the recipient embryo to disable hepatogenesis, and discuss the advantages of using fumarylacetoacetate hydrolase knockouts and other genetic modifications to disable hepatogenesis. Interspecies blastocyst complementation using porcine recipients for primate donors has been achieved, although percentages of chimerism remain persistently low. Recent investigation into the dynamic transcriptomes of pigs and primates have created new opportunities to intimately match the stage of developing animal embryos with one of the many varieties of human induced pluripotent stem cell. We discuss techniques for decreasing donor cell apoptosis, targeting donor tissue to endodermal structures to avoid neural or germline chimerism, and decreasing the immunogenicity of chimeric organs by generating donor endothelium. Elsevier 2021-10-21 /pmc/articles/PMC8581169/ /pubmed/34678209 http://dx.doi.org/10.1016/j.stemcr.2021.09.018 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Perspective Larson, Ellen L. Joo, Dong Jin Nelson, Erek D. Amiot, Bruce P. Aravalli, Rajagopal N. Nyberg, Scott L. Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title | Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title_full | Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title_fullStr | Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title_full_unstemmed | Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title_short | Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
title_sort | fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581169/ https://www.ncbi.nlm.nih.gov/pubmed/34678209 http://dx.doi.org/10.1016/j.stemcr.2021.09.018 |
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