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Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation.

Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al-Akkad W, Longato L, Brown D, Maghsoudlou P, Dhillon AP, Fuller B, Davidson B, Moore K, Dhar D, De Coppi P, Malago M, Pinzani M - Sci Rep (2015)

Bottom Line: Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture.We demonstrate decellularization of human liver and repopulation with derived human liver cells.This is a key advance in bioartificial liver development.

View Article: PubMed Central - PubMed

Affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.

ABSTRACT
Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.

No MeSH data available.


Related in: MedlinePlus

Expression and distribution of ECM proteins.Collagen I, III and IV staining in FL is seen as fine strands in the parenchymal space as well as around the blood vessels (a,b; e,f; I,j). Collagen I and III distribution was preserved following decellularization as demonstrated by a staining in both sinusoids and portal tracts in DL (c,d; g,h). Collagen IV (k,l) and fibronectin (o,p) staining showed a conserved meshwork in sinusoids and biliary ducts after decellularization. Scale bar for 20X magnification (left panel): 100 μm and 40X (right panel): 50 μm.
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f3: Expression and distribution of ECM proteins.Collagen I, III and IV staining in FL is seen as fine strands in the parenchymal space as well as around the blood vessels (a,b; e,f; I,j). Collagen I and III distribution was preserved following decellularization as demonstrated by a staining in both sinusoids and portal tracts in DL (c,d; g,h). Collagen IV (k,l) and fibronectin (o,p) staining showed a conserved meshwork in sinusoids and biliary ducts after decellularization. Scale bar for 20X magnification (left panel): 100 μm and 40X (right panel): 50 μm.

Mentions: The expression and distribution of the extracellular matrix (ECM) of the decellularized liver (DL) scaffold was next analysed, comparing it with ECM of fresh human liver tissue (FL) by immunohistochemistry. This analysis showed that the expression and distribution of key ECM components, namely collagen type I (Fig. 3c,d), collagen type III (Fig. 3g,h), fibronectin (Fig. 3o,p) and collagen IV (Fig. 3k,l) were fully maintained when compared to that detected in FL. Importantly, the pattern of distribution of each ECM component within the DL confirmed the full preservation of the architectural organisation of the original liver tissue (FL).


Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation.

Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al-Akkad W, Longato L, Brown D, Maghsoudlou P, Dhillon AP, Fuller B, Davidson B, Moore K, Dhar D, De Coppi P, Malago M, Pinzani M - Sci Rep (2015)

Expression and distribution of ECM proteins.Collagen I, III and IV staining in FL is seen as fine strands in the parenchymal space as well as around the blood vessels (a,b; e,f; I,j). Collagen I and III distribution was preserved following decellularization as demonstrated by a staining in both sinusoids and portal tracts in DL (c,d; g,h). Collagen IV (k,l) and fibronectin (o,p) staining showed a conserved meshwork in sinusoids and biliary ducts after decellularization. Scale bar for 20X magnification (left panel): 100 μm and 40X (right panel): 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528226&req=5

f3: Expression and distribution of ECM proteins.Collagen I, III and IV staining in FL is seen as fine strands in the parenchymal space as well as around the blood vessels (a,b; e,f; I,j). Collagen I and III distribution was preserved following decellularization as demonstrated by a staining in both sinusoids and portal tracts in DL (c,d; g,h). Collagen IV (k,l) and fibronectin (o,p) staining showed a conserved meshwork in sinusoids and biliary ducts after decellularization. Scale bar for 20X magnification (left panel): 100 μm and 40X (right panel): 50 μm.
Mentions: The expression and distribution of the extracellular matrix (ECM) of the decellularized liver (DL) scaffold was next analysed, comparing it with ECM of fresh human liver tissue (FL) by immunohistochemistry. This analysis showed that the expression and distribution of key ECM components, namely collagen type I (Fig. 3c,d), collagen type III (Fig. 3g,h), fibronectin (Fig. 3o,p) and collagen IV (Fig. 3k,l) were fully maintained when compared to that detected in FL. Importantly, the pattern of distribution of each ECM component within the DL confirmed the full preservation of the architectural organisation of the original liver tissue (FL).

Bottom Line: Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture.We demonstrate decellularization of human liver and repopulation with derived human liver cells.This is a key advance in bioartificial liver development.

View Article: PubMed Central - PubMed

Affiliation: UCL, Institute for Liver and Digestive Health, University College London, London UK.

ABSTRACT
Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development.

No MeSH data available.


Related in: MedlinePlus