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A Patient‐Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum
Author(s) -
Bishi Dillip K.,
Mathapati Santosh,
Venugopal Jayarama R.,
Guhathakurta Soma,
Cherian Kotturathu M.,
Verma Rama S.,
Ramakrishna Seeram
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500897
Subject(s) - ex vivo , hepatocyte growth factor , mesenchymal stem cell , tissue engineering , in vivo , hepatocyte , stem cell , biomedical engineering , liver regeneration , scaffold , bone marrow , nanofiber , microbiology and biotechnology , materials science , in vitro , chemistry , pathology , medicine , biology , regeneration (biology) , biochemistry , nanotechnology , receptor
Design and development of ex vivo bioengineered liver tissue substitutes intended for subsequent in vivo implantation has been considered therapeutically relevant to treat many liver diseases that require whole‐organ replacement on a long‐term basis. The present study focus on patient‐inspired ex vivo liver tissue engineering strategy to generate hepatocyte‐scaffold composite by combining bone marrow mesenchymal stem cells (BMSCs) derived from cardiac failure patients with secondary hyperbilirubinemia as primers of hepatic differentiation and hepatocyte growth factor (HGF)‐enriched sera from same individuals as hepatic inducer. A biodegradable and implantable electrospun fibrous mesh of poly‐ l ‐lactic acid (PLLA) and gelatin is used as supporting matrix (average fiber diameter = 285 ± 64 nm, porosity = 81 ± 4%, and average pore size = 1.65 ± 0.77 μm). The fibrous mesh supports adhesion, proliferation, and hepatic commitment of patient‐derived BMSCs of adequate stemness using HGF‐enriched sera generating metabolically competent hepatocyte‐like cells, which is comparable to the hepatic induction with defined recombinant growth factor cocktail. The observed results confirm the combinatorial effects of nanofiber topography and biochemical cues in guiding hepatic specification of BMSCs. The fibrous mesh‐hepatocyte construct developed in this study using natural growth factors and BMSCs of same individual is promising for future therapeutic applications in treating damaged livers.

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