Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation

Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wn...

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Autores principales:	Nesrine Ebrahim, Omnia A. M. Badr, Mohamed M. Yousef, Amira Hassouna, Dina Sabry, Ayman Samir Farid, Ola Mostafa, Hajir A. Al Saihati, Yasmin Seleem, Eman Abd El Aziz, Ahmed Hassan Khalil, Ahmed Nawar, Ahmed A. Shoulah, Mohammad Aljasir, Amira Zaki Mohamed, Mohamed El-Sherbiny, Nehal M. Elsherbiny, Mohamed Ahmed Eladl, Nicholas Robert Forsyth, Rabab F. Salim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	decellularization recellularization Wnt/<i>β</i>-catenin pathway liver regeneration iPSC regenerative medicine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6ec93d01d00f4961a4936473364a28f9
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spelling	oai:doaj.org-article:6ec93d01d00f4961a4936473364a28f92021-11-25T17:07:33ZFunctional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation10.3390/cells101128192073-4409https://doaj.org/article/6ec93d01d00f4961a4936473364a28f92021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2819https://doaj.org/toc/2073-4409Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. Methods. Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.Nesrine EbrahimOmnia A. M. BadrMohamed M. YousefAmira HassounaDina SabryAyman Samir FaridOla MostafaHajir A. Al SaihatiYasmin SeleemEman Abd El AzizAhmed Hassan KhalilAhmed NawarAhmed A. ShoulahMohammad AljasirAmira Zaki MohamedMohamed El-SherbinyNehal M. ElsherbinyMohamed Ahmed EladlNicholas Robert ForsythRabab F. SalimMDPI AGarticledecellularizationrecellularizationWnt/<i>β</i>-catenin pathwayliver regenerationiPSCregenerative medicineBiology (General)QH301-705.5ENCells, Vol 10, Iss 2819, p 2819 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	decellularization recellularization Wnt/<i>β</i>-catenin pathway liver regeneration iPSC regenerative medicine Biology (General) QH301-705.5
spellingShingle	decellularization recellularization Wnt/<i>β</i>-catenin pathway liver regeneration iPSC regenerative medicine Biology (General) QH301-705.5 Nesrine Ebrahim Omnia A. M. Badr Mohamed M. Yousef Amira Hassouna Dina Sabry Ayman Samir Farid Ola Mostafa Hajir A. Al Saihati Yasmin Seleem Eman Abd El Aziz Ahmed Hassan Khalil Ahmed Nawar Ahmed A. Shoulah Mohammad Aljasir Amira Zaki Mohamed Mohamed El-Sherbiny Nehal M. Elsherbiny Mohamed Ahmed Eladl Nicholas Robert Forsyth Rabab F. Salim Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
description	Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. Methods. Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.
format	article
author	Nesrine Ebrahim Omnia A. M. Badr Mohamed M. Yousef Amira Hassouna Dina Sabry Ayman Samir Farid Ola Mostafa Hajir A. Al Saihati Yasmin Seleem Eman Abd El Aziz Ahmed Hassan Khalil Ahmed Nawar Ahmed A. Shoulah Mohammad Aljasir Amira Zaki Mohamed Mohamed El-Sherbiny Nehal M. Elsherbiny Mohamed Ahmed Eladl Nicholas Robert Forsyth Rabab F. Salim
author_facet	Nesrine Ebrahim Omnia A. M. Badr Mohamed M. Yousef Amira Hassouna Dina Sabry Ayman Samir Farid Ola Mostafa Hajir A. Al Saihati Yasmin Seleem Eman Abd El Aziz Ahmed Hassan Khalil Ahmed Nawar Ahmed A. Shoulah Mohammad Aljasir Amira Zaki Mohamed Mohamed El-Sherbiny Nehal M. Elsherbiny Mohamed Ahmed Eladl Nicholas Robert Forsyth Rabab F. Salim
author_sort	Nesrine Ebrahim
title	Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
title_short	Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
title_full	Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
title_fullStr	Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
title_full_unstemmed	Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
title_sort	functional recellularization of acellular rat liver scaffold by induced pluripotent stem cells: molecular evidence for wnt/b-catenin upregulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6ec93d01d00f4961a4936473364a28f9
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Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation

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