title: A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum.
abstract: 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.
authors.affiliation: Centre for Nanofibers and Nanotechnology, E3 # 05-12, Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, 117576, Singapore.|Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai, 600101, India.|Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India.
authors.forename: Dillip K
authors.initials: DK
authors.lastname: Bishi
authors.affiliation: Centre for Nanofibers and Nanotechnology, E3 # 05-12, Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, 117576, Singapore.|Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai, 600101, India.|Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Mathapati
authors.affiliation: Centre for Nanofibers and Nanotechnology, E3 # 05-12, Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, 117576, Singapore.
authors.forename: Jayarama R
authors.initials: JR
authors.lastname: Venugopal
authors.affiliation: Department of Engineering Design, Indian Institute of Technology Madras, Chennai, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Guhathakurta
authors.affiliation: Stem Cells and Tissue Engineering Laboratory, International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai, 600101, India.
authors.forename: Kotturathu M
authors.initials: KM
authors.lastname: Cherian
authors.affiliation: Stem Cells and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India.
authors.forename: Rama S
authors.initials: RS
authors.lastname: Verma
authors.affiliation: Centre for Nanofibers and Nanotechnology, E3 # 05-12, Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, 117576, Singapore.
authors.forename: Seeram
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000368:Aged; D064592:Autografts; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism / Q000628:therapy; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D011091:Polyesters / Q000737:chemistry; D044967:Serum; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C066855:HGF protein, human; D011091:Polyesters; C033616:poly(lactide); D017228:Hepatocyte Growth Factor
keywords: cardiac failure; electrospinning; hepatocyte growth factor; hyperbilirubinemia; mesenchymal stem cells