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Decellularized amniotic membrane Scaffolds improve differentiation of iPSCs to functional hepatocyte-like cells |
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| Authors: | Mohammad Foad Abazari Fatemeh Soleimanifar Seyed Ehsan Enderami Navid Nasiri Fatemeh Nejati Seyed Ahmad Mousavi Masoud Soleimani Jafar Kiani Pegah Ghoraeian Mousa Kehtari |
| Affiliation: | 1. Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran Mohammad Foad Abazari and Fatemeh Soleimanifar contributed equally to this work.;2. Department of Medical Biotechnology, Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran;3. Immunogenetics Research Center, Department of Medical Biotechnolmicroogy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;4. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran;5. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;6. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;7. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran;8. Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran;9. Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran |
| Abstract: | Human-induced pluripotent stem cells-derived hepatocyte-like cells (hiPSCs-HLCs) holds considerable promise for future clinical personalized therapy of liver disease. However, the low engraftment of these cells in the damaged liver microenvironment is still an obstacle for potential application. In this study, we explored the effectiveness of decellularized amniotic membrane (dAM) matrices for culturing of iPSCs and promoting their differentiation into HLCs. The DNA content assay and histological evaluation indicated that cellular and nuclear residues were efficiently eliminated and the AM extracellular matrix component was maintained during decelluarization. DAM matrices were developed as three-dimensional scaffolds and hiPSCs were seeded into these scaffolds in defined induction media. In dAM scaffolds, hiPSCs-HLCs gradually took a typical shape of hepatocytes (polygonal morphology). HiPSCs-HLCs that were cultured into dAM scaffolds showed a higher level of hepatic markers than those cultured in tissue culture plates (TCPs). Moreover, functional activities in term of albumin and urea synthesis and CYP3A activity were significantly higher in dAM scaffolds than TCPs over the same differentiation period. Thus, based on our results, dAM scaffold might have a considerable potential in liver tissue engineering, because it can improve hepatic differentiation of hiPSCs which exhibited higher level of the hepatic marker and more stable metabolic functions. |
| Keywords: | amniotic membrane decellularized scaffold hepatic differentiation human-induced pluripotent stem cells liver tissue engineering |