Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure
Abstract Background Hepatocyte transplantation has been proposed as an effective treatment for patients with acute liver failure (ALF), but its application is limited by a severe shortage of donor livers. Human pluripotent stem cells (hPSCs) have emerged as a potential cell source for regenerative m...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-1063-2 |
| _version_ | 1811208405788917760 |
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| author | Quan-Wen Liu Qian-Yu Liu Jing-Yuan Li Li Wei Kang-Kang Ren Xiang-Cheng Zhang Ting Ding Ling Xiao Wen-Jie Zhang Han-You Wu Hong-Bo Xin |
| author_facet | Quan-Wen Liu Qian-Yu Liu Jing-Yuan Li Li Wei Kang-Kang Ren Xiang-Cheng Zhang Ting Ding Ling Xiao Wen-Jie Zhang Han-You Wu Hong-Bo Xin |
| author_sort | Quan-Wen Liu |
| collection | DOAJ |
| description | Abstract Background Hepatocyte transplantation has been proposed as an effective treatment for patients with acute liver failure (ALF), but its application is limited by a severe shortage of donor livers. Human pluripotent stem cells (hPSCs) have emerged as a potential cell source for regenerative medicine. Human amniotic epithelial stem cells (hAESCs) derived from amniotic membrane have multilineage differentiation potential which makes them suitable for possible application in hepatocyte regeneration and ALF treatment. Methods The pluripotent characteristics, immunogenicity, and tumorigenicity of hAESCs were studied by various methods. hAESCs were differentiated to hepatocyte-like cells (HLCs) using a non-transgenic and three-step induction protocol. ALB secretion, urea production, periodic acid-Schiff staining, and ICG uptake were performed to investigate the function of HLCs. The HLCs were transplanted into ALF NOD-SCID (nonobese diabetic severe combined immunodeficient) mouse, and the therapeutic effects were determined via liver function test, histopathology, and survival rate analysis. The ability of HLCs to engraft the damaged liver was evaluated by detecting the presence of GFP-positive cells. Results hAESCs expressed various markers of embryonic stem cells, epithelial stem cells, and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAESC-derived hepatocytes possess the similar functions of human primary hepatocytes (hPH) such as producing urea, secreting ALB, uptaking ICG, storing glycogen, and expressing CYP enzymes. HLC transplantation via the tail vein could engraft in live parenchymal, improve the liver function, and protect hepatic injury from CCl4-induced ALF in mice. More importantly, HLC transplantation was able to significantly prolong the survival of ALF mouse. Conclusion We have established a rapid and efficient differentiation protocol that is able to successfully generate ample functional HLCs from hAESCs, in which the liver injuries and death rate of CCl4-induced ALF mouse can be significantly rescued by HLC transplantation. Therefore, our results may offer a superior approach for treating ALF. |
| first_indexed | 2024-04-12T04:20:42Z |
| format | Article |
| id | doaj.art-06e37748eb7545e0b6268f44b03ac66b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-12T04:20:42Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-06e37748eb7545e0b6268f44b03ac66b2022-12-22T03:48:15ZengBMCStem Cell Research & Therapy1757-65122018-11-019111510.1186/s13287-018-1063-2Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failureQuan-Wen Liu0Qian-Yu Liu1Jing-Yuan Li2Li Wei3Kang-Kang Ren4Xiang-Cheng Zhang5Ting Ding6Ling Xiao7Wen-Jie Zhang8Han-You Wu9Hong-Bo Xin10Institute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityInstitute of Translational Medicine, Nanchang UniversityAbstract Background Hepatocyte transplantation has been proposed as an effective treatment for patients with acute liver failure (ALF), but its application is limited by a severe shortage of donor livers. Human pluripotent stem cells (hPSCs) have emerged as a potential cell source for regenerative medicine. Human amniotic epithelial stem cells (hAESCs) derived from amniotic membrane have multilineage differentiation potential which makes them suitable for possible application in hepatocyte regeneration and ALF treatment. Methods The pluripotent characteristics, immunogenicity, and tumorigenicity of hAESCs were studied by various methods. hAESCs were differentiated to hepatocyte-like cells (HLCs) using a non-transgenic and three-step induction protocol. ALB secretion, urea production, periodic acid-Schiff staining, and ICG uptake were performed to investigate the function of HLCs. The HLCs were transplanted into ALF NOD-SCID (nonobese diabetic severe combined immunodeficient) mouse, and the therapeutic effects were determined via liver function test, histopathology, and survival rate analysis. The ability of HLCs to engraft the damaged liver was evaluated by detecting the presence of GFP-positive cells. Results hAESCs expressed various markers of embryonic stem cells, epithelial stem cells, and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAESC-derived hepatocytes possess the similar functions of human primary hepatocytes (hPH) such as producing urea, secreting ALB, uptaking ICG, storing glycogen, and expressing CYP enzymes. HLC transplantation via the tail vein could engraft in live parenchymal, improve the liver function, and protect hepatic injury from CCl4-induced ALF in mice. More importantly, HLC transplantation was able to significantly prolong the survival of ALF mouse. Conclusion We have established a rapid and efficient differentiation protocol that is able to successfully generate ample functional HLCs from hAESCs, in which the liver injuries and death rate of CCl4-induced ALF mouse can be significantly rescued by HLC transplantation. Therefore, our results may offer a superior approach for treating ALF.http://link.springer.com/article/10.1186/s13287-018-1063-2Acute liver failureHuman amniotic epithelial stem cellsHepatocyte-like cellsHuman primary hepatocytesCell transplantation |
| spellingShingle | Quan-Wen Liu Qian-Yu Liu Jing-Yuan Li Li Wei Kang-Kang Ren Xiang-Cheng Zhang Ting Ding Ling Xiao Wen-Jie Zhang Han-You Wu Hong-Bo Xin Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure Stem Cell Research & Therapy Acute liver failure Human amniotic epithelial stem cells Hepatocyte-like cells Human primary hepatocytes Cell transplantation |
| title | Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure |
| title_full | Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure |
| title_fullStr | Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure |
| title_full_unstemmed | Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure |
| title_short | Therapeutic efficiency of human amniotic epithelial stem cell-derived functional hepatocyte-like cells in mice with acute hepatic failure |
| title_sort | therapeutic efficiency of human amniotic epithelial stem cell derived functional hepatocyte like cells in mice with acute hepatic failure |
| topic | Acute liver failure Human amniotic epithelial stem cells Hepatocyte-like cells Human primary hepatocytes Cell transplantation |
| url | http://link.springer.com/article/10.1186/s13287-018-1063-2 |
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