AIM: To investigate the biochemical and functional properties of a rat acellular pancreatic bioscaffold (APB). METHODS: Fresh pancreata were soaked and perfused. The histological structure, the extracellular matrix (ECM) composition, and the DNA content of the APBs were evaluated. After biocompatibility studies, the proliferation, apoptosis and differentiation of AR42J pancreatic acinar cells cultured on APBs were assessed. RESULTS: The pancreatic tissues became translucent after decellularization. The native macroscopic 3D architecture and the ECM ultrastructure were preserved, with large ductal structures and vascular tissue branching from the greater pancreatic artery, but there were no visible vascular endothelial cells, cellular components or cracked cellular debris. The ECM components, including collagen I, collagen IV, fibronectin, laminin and sGAG, were not decreased after decellularization of the APB (P>0.05); however, the DNA content was decreased significantly (P<0.05). The subcutaneous implantation sites showed low immunological response and low cytotoxicity around the APB. The proliferation rate was higher and the apoptosis rate was lower when AR42J cells were cultured on APB than when they were cultured in media alone, on artificial scaffold or ECM (P<0.05). The gene expression of pancreatic duodenal homeodomain containing transcription factor (PDX-1) and pancreatic exocrine transcription factor (PTF-1) and the protein expression of alpha-Amy, cytokeratin 7 (CK7) and fetal liver kinase-1 (Flk-1) were higher for the APB group than for the other groups (P<0.001). CONCLUSION: Our findings support the biological utility of whole pancreas APBs as biomaterial scaffolds, which provides an improved approach for regenerative medicine.
机构:
UCL, Div Surg & Intervent Sci, London NW3 2PF, England
UCL, Dept Med Phys & Bioengn, London WC1E 6BT, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Ricketts, Kate P. M.
Cheema, Umber
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UCL, Div Surg & Intervent Sci, London NW3 2PF, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Cheema, Umber
Nyga, Agata
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UCL, Div Surg & Intervent Sci, London NW3 2PF, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Nyga, Agata
Castoldi, Andrea
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Politecn Milan, Dipartimento Elettron & Informaz, I-20133 Milan, Italy
Inst Nazl Fis Nucl, Sez Milano, Milan, ItalyUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Castoldi, Andrea
Guazzoni, Chiara
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Politecn Milan, Dipartimento Elettron & Informaz, I-20133 Milan, Italy
Inst Nazl Fis Nucl, Sez Milano, Milan, ItalyUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Guazzoni, Chiara
Magdeldin, Tarig
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UCL, Div Surg & Intervent Sci, London NW3 2PF, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Magdeldin, Tarig
Emberton, Mark
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UCL, Div Surg & Intervent Sci, London NW3 2PF, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Emberton, Mark
Gibson, Adam P.
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UCL, Dept Med Phys & Bioengn, London WC1E 6BT, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Gibson, Adam P.
Royle, Gary J.
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UCL, Dept Med Phys & Bioengn, London WC1E 6BT, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
Royle, Gary J.
Loizidou, Marilena
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UCL, Div Surg & Intervent Sci, London NW3 2PF, EnglandUCL, Div Surg & Intervent Sci, London NW3 2PF, England
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Finkel, Samuel
Sweet, Shannon
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Sweet, Shannon
Locke, Tyler
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Locke, Tyler
Smith, Sydney
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Smith, Sydney
Wang, Zhefan
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Wang, Zhefan
Sandini, Christopher
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA
Sandini, Christopher
Imredy, John
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Merck & Co Inc, Vitro Safety Pharmacol Genet & Cellular Toxicol, Rahway, NJ 07065 USAFluidForm Inc, Waltham, MA 02451 USA
Imredy, John
He, Yufang
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Merck & Co Inc, Div Technol Infrastruct Operat & Experience, Rahway, NJ 07065 USAFluidForm Inc, Waltham, MA 02451 USA
He, Yufang
Durante, Marc
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Merck & Co Inc, Div Technol Infrastruct Operat & Experience, Rahway, NJ 07065 USAFluidForm Inc, Waltham, MA 02451 USA
Durante, Marc
Lagrutta, Armando
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Merck & Co Inc, Vitro Safety Pharmacol Genet & Cellular Toxicol, Rahway, NJ 07065 USAFluidForm Inc, Waltham, MA 02451 USA
Lagrutta, Armando
Feinberg, Adam
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FluidForm Inc, Waltham, MA 02451 USA
Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA
Carnegie Mellon Univ, Dept Mat Sci & Engn, Pittsburgh, PA 15213 USAFluidForm Inc, Waltham, MA 02451 USA
Feinberg, Adam
Lee, Andrew
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FluidForm Inc, Waltham, MA 02451 USAFluidForm Inc, Waltham, MA 02451 USA