A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum

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 vi...

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Veröffentlicht in:Advanced healthcare materials 2016-05, Vol.5 (9), p.1058-1070
Hauptverfasser: Bishi, Dillip K., Mathapati, Santosh, Venugopal, Jayarama R., Guhathakurta, Soma, Cherian, Kotturathu M., Verma, Rama S., Ramakrishna, Seeram
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container_end_page 1070
container_issue 9
container_start_page 1058
container_title Advanced healthcare materials
container_volume 5
creator Bishi, Dillip K.
Mathapati, Santosh
Venugopal, Jayarama R.
Guhathakurta, Soma
Cherian, Kotturathu M.
Verma, Rama S.
Ramakrishna, Seeram
description 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. Development of a patient‐inspired hepatocyte‐scaffold composite is reported. Hepatocyte‐growth‐factor‐enriched sera obtained from cardiac failure patients with secondary hyperbilirubinemia are used to induce hepatic commitment of bone‐marrow‐derived mesenchymal stem cells of same individuals on an electrospun fibrous mesh of poly‐l‐lactic acid (PLLA)/gelatin. This generates metabolically competent hepatocyte‐like cells on fibrous scaffolds, which can have future therapeutic implication to restore damaged liver functions.
doi_str_mv 10.1002/adhm.201500897
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Healthcare Mater</addtitle><date>2016-05</date><risdate>2016</risdate><volume>5</volume><issue>9</issue><spage>1058</spage><epage>1070</epage><pages>1058-1070</pages><issn>2192-2640</issn><eissn>2192-2659</eissn><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. 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subjects Aged
Autografts
cardiac failure
Damage
Electrospinning
Extracellular Matrix - chemistry
Failure
Female
Growth factors
hepatocyte growth factor
Hepatocyte Growth Factor - pharmacology
Hepatocytes - cytology
Hepatocytes - metabolism
Humans
hyperbilirubinemia
Liver
Liver - cytology
Liver - metabolism
Liver Diseases - metabolism
Liver Diseases - therapy
Male
mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Middle Aged
Patients
Polyesters - chemistry
Polylactic acid
Serum
Stem cells
Tissue Engineering - methods
title A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum
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