Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology
Although several types of somatic cells have been reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte-like cells (iHeps), the method for generating such cells from renal tubular epithelial cells shed in human urine and transplanting them into animal livers...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2016-12-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368916X692014 |
| _version_ | 1818446143358500864 |
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| author | Vanessa Sauer Tatyana Tchaikovskaya Xia Wang Yanfeng Li Wei Zhang Krisztina Tar Zsuzsanna Polgar Jianqiang Ding Chandan Guha Ira J. Fox Namita Roy-Chowdhury Jayanta Roy-Chowdhury |
| author_facet | Vanessa Sauer Tatyana Tchaikovskaya Xia Wang Yanfeng Li Wei Zhang Krisztina Tar Zsuzsanna Polgar Jianqiang Ding Chandan Guha Ira J. Fox Namita Roy-Chowdhury Jayanta Roy-Chowdhury |
| author_sort | Vanessa Sauer |
| collection | DOAJ |
| description | Although several types of somatic cells have been reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte-like cells (iHeps), the method for generating such cells from renal tubular epithelial cells shed in human urine and transplanting them into animal livers has not been described systematically. We report reprogramming of human urinary epithelial cells into iPSCs and subsequent hepatic differentiation, followed by a detailed characterization of the newly generated iHeps. The epithelial cells were reprogrammed into iPSCs by delivering the pluripotency factors OCT3/4, SOX2, KLF4, and MYC using methods that do not involve transgene integration, such as nucleofection of episomal (oriP/EBNA-1) plasmids or infection with recombinant Sendai viruses. After characterization of stable iPSC lines, a three-step differentiation toward hepatocytes was performed. The iHeps expressed a large number of hepatocyte-preferred genes, including nuclear receptors that regulate genes involved in cholesterol homeostasis, bile acid transport, and detoxification. MicroRNA profile of the iHeps largely paralleled that of primary human hepatocytes. The iHeps engrafted into the livers of Scid mice transgenic for mutant human SERPINA1 after intrasplenic injection. Thus, urine is a readily available source for generating human iHeps that could be potentially useful for disease modeling, pharmacological development, and regenerative medicine. |
| first_indexed | 2024-12-14T19:43:02Z |
| format | Article |
| id | doaj.art-0140d9d8c7d04cf8ba40359824a27037 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-14T19:43:02Z |
| publishDate | 2016-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-0140d9d8c7d04cf8ba40359824a270372022-12-21T22:49:38ZengSAGE PublishingCell Transplantation0963-68971555-38922016-12-012510.3727/096368916X692014Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell TechnologyVanessa Sauer0Tatyana Tchaikovskaya1Xia Wang2Yanfeng Li3Wei Zhang4Krisztina Tar5Zsuzsanna Polgar6Jianqiang Ding7Chandan Guha8Ira J. Fox9Namita Roy-Chowdhury10Jayanta Roy-Chowdhury11Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USADepartment of Pathology, Albert Einstein College of Medicine, NY, New York, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USAMarion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, NY, USADepartment of Pathology, Albert Einstein College of Medicine, NY, New York, USADepartment of Surgery and McGowan Institute for Regenerative Medicine, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USADepartment of Genetics, Albert Einstein College of Medicine, New York, NY, USADepartment of Genetics, Albert Einstein College of Medicine, New York, NY, USAAlthough several types of somatic cells have been reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte-like cells (iHeps), the method for generating such cells from renal tubular epithelial cells shed in human urine and transplanting them into animal livers has not been described systematically. We report reprogramming of human urinary epithelial cells into iPSCs and subsequent hepatic differentiation, followed by a detailed characterization of the newly generated iHeps. The epithelial cells were reprogrammed into iPSCs by delivering the pluripotency factors OCT3/4, SOX2, KLF4, and MYC using methods that do not involve transgene integration, such as nucleofection of episomal (oriP/EBNA-1) plasmids or infection with recombinant Sendai viruses. After characterization of stable iPSC lines, a three-step differentiation toward hepatocytes was performed. The iHeps expressed a large number of hepatocyte-preferred genes, including nuclear receptors that regulate genes involved in cholesterol homeostasis, bile acid transport, and detoxification. MicroRNA profile of the iHeps largely paralleled that of primary human hepatocytes. The iHeps engrafted into the livers of Scid mice transgenic for mutant human SERPINA1 after intrasplenic injection. Thus, urine is a readily available source for generating human iHeps that could be potentially useful for disease modeling, pharmacological development, and regenerative medicine.https://doi.org/10.3727/096368916X692014 |
| spellingShingle | Vanessa Sauer Tatyana Tchaikovskaya Xia Wang Yanfeng Li Wei Zhang Krisztina Tar Zsuzsanna Polgar Jianqiang Ding Chandan Guha Ira J. Fox Namita Roy-Chowdhury Jayanta Roy-Chowdhury Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology Cell Transplantation |
| title | Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology |
| title_full | Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology |
| title_fullStr | Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology |
| title_full_unstemmed | Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology |
| title_short | Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells Using Stem Cell Technology |
| title_sort | human urinary epithelial cells as a source of engraftable hepatocyte like cells using stem cell technology |
| url | https://doi.org/10.3727/096368916X692014 |
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