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“iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives”
The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) culture...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880334/ https://www.ncbi.nlm.nih.gov/pubmed/36711019 http://dx.doi.org/10.3389/fphys.2023.1094249 |
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author | Roman, Giacomo Stavik, Benedicte Lauritzen, Knut H. Sandset, Per Morten Harrison, Sean P. Sullivan, Gareth J. Chollet, Maria Eugenia |
author_facet | Roman, Giacomo Stavik, Benedicte Lauritzen, Knut H. Sandset, Per Morten Harrison, Sean P. Sullivan, Gareth J. Chollet, Maria Eugenia |
author_sort | Roman, Giacomo |
collection | PubMed |
description | The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease. |
format | Online Article Text |
id | pubmed-9880334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98803342023-01-28 “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” Roman, Giacomo Stavik, Benedicte Lauritzen, Knut H. Sandset, Per Morten Harrison, Sean P. Sullivan, Gareth J. Chollet, Maria Eugenia Front Physiol Physiology The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease. Frontiers Media S.A. 2023-01-13 /pmc/articles/PMC9880334/ /pubmed/36711019 http://dx.doi.org/10.3389/fphys.2023.1094249 Text en Copyright © 2023 Roman, Stavik, Lauritzen, Sandset, Harrison, Sullivan and Chollet. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Roman, Giacomo Stavik, Benedicte Lauritzen, Knut H. Sandset, Per Morten Harrison, Sean P. Sullivan, Gareth J. Chollet, Maria Eugenia “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title | “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title_full | “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title_fullStr | “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title_full_unstemmed | “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title_short | “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives” |
title_sort | “ipsc-derived liver organoids and inherited bleeding disorders: potential and future perspectives” |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880334/ https://www.ncbi.nlm.nih.gov/pubmed/36711019 http://dx.doi.org/10.3389/fphys.2023.1094249 |
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