Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins

Abstract The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation ha...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Francis D. Gratte, Sara Pasic, John K. Olynyk, George C. T. Yeoh, David Tosh, Deirdre R. Coombe, Janina E. E. Tirnitz-Parker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c6f068c1e694afea2169b275e22b469
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1c6f068c1e694afea2169b275e22b469
record_format	dspace
spelling	oai:doaj.org-article:1c6f068c1e694afea2169b275e22b4692021-12-02T15:08:50ZTransdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins10.1038/s41598-018-22596-z2045-2322https://doaj.org/article/1c6f068c1e694afea2169b275e22b4692018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22596-zhttps://doaj.org/toc/2045-2322Abstract The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin- or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.Francis D. GratteSara PasicJohn K. OlynykGeorge C. T. YeohDavid ToshDeirdre R. CoombeJanina E. E. Tirnitz-ParkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francis D. Gratte Sara Pasic John K. Olynyk George C. T. Yeoh David Tosh Deirdre R. Coombe Janina E. E. Tirnitz-Parker Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
description	Abstract The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin- or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.
format	article
author	Francis D. Gratte Sara Pasic John K. Olynyk George C. T. Yeoh David Tosh Deirdre R. Coombe Janina E. E. Tirnitz-Parker
author_facet	Francis D. Gratte Sara Pasic John K. Olynyk George C. T. Yeoh David Tosh Deirdre R. Coombe Janina E. E. Tirnitz-Parker
author_sort	Francis D. Gratte
title	Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
title_short	Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
title_full	Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
title_fullStr	Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
title_full_unstemmed	Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
title_sort	transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1c6f068c1e694afea2169b275e22b469
work_keys_str_mv	AT francisdgratte transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT sarapasic transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT johnkolynyk transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT georgectyeoh transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT davidtosh transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT deirdrercoombe transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins AT janinaeetirnitzparker transdifferentiationofpancreaticprogenitorcellstohepatocytelikecellsisnotserumdependentwhenfacilitatedbyextracellularmatrixproteins
_version_	1718387986500943872

Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins

Ejemplares similares