Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes
In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that, in vivo, characterizes their correspondent organ and tiss...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/5481493 |
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| author | Angela Maria Cozzolino Valeria Noce Cecilia Battistelli Alessandra Marchetti Germana Grassi Carla Cicchini Marco Tripodi Laura Amicone |
| author_facet | Angela Maria Cozzolino Valeria Noce Cecilia Battistelli Alessandra Marchetti Germana Grassi Carla Cicchini Marco Tripodi Laura Amicone |
| author_sort | Angela Maria Cozzolino |
| collection | DOAJ |
| description | In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that, in vivo, characterizes their correspondent organ and tissue. In the liver, the stromal rigidity is essential to obtain the correct organ physiology whereas any alteration causes liver cell dysfunctions. The rigidity of the substrate is an element no longer negligible for the cultivation of several cell types, so that many data so far obtained, where cells have been cultured on plastic, could be revised. Regarding liver cells, standard culture conditions lead to the dedifferentiation of primary hepatocytes, transdifferentiation of stellate cells into myofibroblasts, and loss of fenestration of sinusoidal endothelium. Furthermore, standard cultivation of liver stem/precursor cells impedes an efficient execution of the epithelial/hepatocyte differentiation program, leading to the expansion of a cell population expressing only partially liver functions and products. Overcoming these limitations is mandatory for any approach of liver tissue engineering. Here we propose cell lines as in vitro models of liver stem cells and hepatocytes and an innovative culture method that takes into account the substrate stiffness to obtain, respectively, a rapid and efficient differentiation process and the maintenance of the fully differentiated phenotype. |
| format | Article |
| id | doaj-art-68649dff1ebe460bb7b39ba73f80014c |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-68649dff1ebe460bb7b39ba73f80014c2025-08-20T03:34:03ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/54814935481493Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of HepatocytesAngela Maria Cozzolino0Valeria Noce1Cecilia Battistelli2Alessandra Marchetti3Germana Grassi4Carla Cicchini5Marco Tripodi6Laura Amicone7Department of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyNational Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyDepartment of Cellular Biotechnologies and Hematology, Section of Molecular Genetics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, ItalyIn many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that, in vivo, characterizes their correspondent organ and tissue. In the liver, the stromal rigidity is essential to obtain the correct organ physiology whereas any alteration causes liver cell dysfunctions. The rigidity of the substrate is an element no longer negligible for the cultivation of several cell types, so that many data so far obtained, where cells have been cultured on plastic, could be revised. Regarding liver cells, standard culture conditions lead to the dedifferentiation of primary hepatocytes, transdifferentiation of stellate cells into myofibroblasts, and loss of fenestration of sinusoidal endothelium. Furthermore, standard cultivation of liver stem/precursor cells impedes an efficient execution of the epithelial/hepatocyte differentiation program, leading to the expansion of a cell population expressing only partially liver functions and products. Overcoming these limitations is mandatory for any approach of liver tissue engineering. Here we propose cell lines as in vitro models of liver stem cells and hepatocytes and an innovative culture method that takes into account the substrate stiffness to obtain, respectively, a rapid and efficient differentiation process and the maintenance of the fully differentiated phenotype.http://dx.doi.org/10.1155/2016/5481493 |
| spellingShingle | Angela Maria Cozzolino Valeria Noce Cecilia Battistelli Alessandra Marchetti Germana Grassi Carla Cicchini Marco Tripodi Laura Amicone Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes Stem Cells International |
| title | Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes |
| title_full | Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes |
| title_fullStr | Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes |
| title_full_unstemmed | Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes |
| title_short | Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes |
| title_sort | modulating the substrate stiffness to manipulate differentiation of resident liver stem cells and to improve the differentiation state of hepatocytes |
| url | http://dx.doi.org/10.1155/2016/5481493 |
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