Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells
As an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins c...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116300237 |
| _version_ | 1811299242505928704 |
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| author | Janet Lawandi Chang Tao Binhai Ren Paul Williams Dora Ling M Anne Swan Najah T Nassif Fraser R Torpy Bronwyn A O'Brien Ann M Simpson |
| author_facet | Janet Lawandi Chang Tao Binhai Ren Paul Williams Dora Ling M Anne Swan Najah T Nassif Fraser R Torpy Bronwyn A O'Brien Ann M Simpson |
| author_sort | Janet Lawandi |
| collection | DOAJ |
| description | As an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins cells with human islet glucokinase, the resultant Melligen cells secreted insulin in response to glucose within the physiological range; commencing at 4.25 mmol/l. Melligen cells exhibited increased glucokinase enzymatic activity in response to physiological glucose concentrations, as compared with Huh7ins cells. When transplanted into diabetic immunoincompetent mice, Melligen cells restored normoglycemia. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that both cell lines expressed a range of β-cell transcription factors and pancreatic hormones. Exposure of Melligen and Huh7ins cells to proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) affected neither their viability nor their ability to secrete insulin to glucose. Gene expression (microarray and qRT-PCR) analyses indicated the survival of Melligen cells in the presence of known β-cell cytotoxins was associated with the expression of NF-κB and antiapoptotic genes (such as BIRC3). This study describes the successful generation of an artificial β-cell line, which, if encapsulated to avoid allograft rejection, may offer a clinically applicable cure for T1D. |
| first_indexed | 2024-04-13T06:32:20Z |
| format | Article |
| id | doaj.art-d6ed86ffb2e34f5db83a856612ee11ab |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-13T06:32:20Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-d6ed86ffb2e34f5db83a856612ee11ab2022-12-22T02:58:05ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012015-01-012Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cellsJanet Lawandi0Chang Tao1Binhai Ren2Paul Williams3Dora Ling4M Anne Swan5Najah T Nassif6Fraser R Torpy7Bronwyn A O'Brien8Ann M Simpson9School of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaDepartment of Endocrinology, University of Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaSchool of Medical Sciences (Anatomy & Histology) and Bosch Institute, University of Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaSchool of the Environment, University of Technology Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaSchool of Medical and Molecular Biosciences and Centre for Health Technologies, University of Technology Sydney, Sydney, AustraliaAs an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins cells with human islet glucokinase, the resultant Melligen cells secreted insulin in response to glucose within the physiological range; commencing at 4.25 mmol/l. Melligen cells exhibited increased glucokinase enzymatic activity in response to physiological glucose concentrations, as compared with Huh7ins cells. When transplanted into diabetic immunoincompetent mice, Melligen cells restored normoglycemia. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that both cell lines expressed a range of β-cell transcription factors and pancreatic hormones. Exposure of Melligen and Huh7ins cells to proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) affected neither their viability nor their ability to secrete insulin to glucose. Gene expression (microarray and qRT-PCR) analyses indicated the survival of Melligen cells in the presence of known β-cell cytotoxins was associated with the expression of NF-κB and antiapoptotic genes (such as BIRC3). This study describes the successful generation of an artificial β-cell line, which, if encapsulated to avoid allograft rejection, may offer a clinically applicable cure for T1D.http://www.sciencedirect.com/science/article/pii/S2329050116300237 |
| spellingShingle | Janet Lawandi Chang Tao Binhai Ren Paul Williams Dora Ling M Anne Swan Najah T Nassif Fraser R Torpy Bronwyn A O'Brien Ann M Simpson Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells Molecular Therapy: Methods & Clinical Development |
| title | Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells |
| title_full | Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells |
| title_fullStr | Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells |
| title_full_unstemmed | Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells |
| title_short | Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells |
| title_sort | reversal of diabetes following transplantation of an insulin secreting human liver cell line melligen cells |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116300237 |
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