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Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids

Willemse, Jorke ; van Tienderen, Gilles ; van Hengel, Eline ; Schurink, Ivo ; van der Ven, Diana ; Kan, Yik ; de Ruiter, Petra ; Rosmark, Oskar LU orcid ; Westergren-Thorsson G, Gunilla LU orcid and Schneeberger, Kerstin , et al. (2022) In Biomaterials 284.
Abstract

Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not... (More)

Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.

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publication status
published
subject
keywords
Extracellular matrix based hydrogel, Hepatobiliary tissue engineering and regenerative medicine, Human intrahepatic cholangiocyte organoids, Liver extracellular matrix extracts, Whole organ perfusion-based liver decellularization
in
Biomaterials
volume
284
article number
121473
publisher
Elsevier
external identifiers
  • pmid:35344800
  • scopus:85126983567
ISSN
0142-9612
DOI
10.1016/j.biomaterials.2022.121473
language
English
LU publication?
yes
id
62adf836-56d8-4447-9967-3e95e632192d
date added to LUP
2022-04-19 12:48:30
date last changed
2024-09-09 01:46:28
@article{62adf836-56d8-4447-9967-3e95e632192d,
  abstract     = {{<p>Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.</p>}},
  author       = {{Willemse, Jorke and van Tienderen, Gilles and van Hengel, Eline and Schurink, Ivo and van der Ven, Diana and Kan, Yik and de Ruiter, Petra and Rosmark, Oskar and Westergren-Thorsson G, Gunilla and Schneeberger, Kerstin and van der Eerden, Bram and Roest, Henk and Spee, Bart and van der Laan, Luc and de Jonge, Jeroen and Verstegen, Monique}},
  issn         = {{0142-9612}},
  keywords     = {{Extracellular matrix based hydrogel; Hepatobiliary tissue engineering and regenerative medicine; Human intrahepatic cholangiocyte organoids; Liver extracellular matrix extracts; Whole organ perfusion-based liver decellularization}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biomaterials}},
  title        = {{Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids}},
  url          = {{http://dx.doi.org/10.1016/j.biomaterials.2022.121473}},
  doi          = {{10.1016/j.biomaterials.2022.121473}},
  volume       = {{284}},
  year         = {{2022}},
}