Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation
Abstract Background This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament an...
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Elsevier
2022-06-01
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Series: | Journal of Genetic Engineering and Biotechnology |
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Online Access: | https://doi.org/10.1186/s43141-022-00369-6 |
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author | Riham M. Aly Hadeer A. Aglan Ghada Nour Eldeen Nadia S. Mahmoud Eman H. Aboul-Ezz Hanaa H. Ahmed |
author_facet | Riham M. Aly Hadeer A. Aglan Ghada Nour Eldeen Nadia S. Mahmoud Eman H. Aboul-Ezz Hanaa H. Ahmed |
author_sort | Riham M. Aly |
collection | DOAJ |
description | Abstract Background This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament and were induced to differentiate into insulin-producing cells (IPCs) using laminin-based differentiation protocol for 14 days. Confirmation of IPCs was performed through real-time PCR analysis and insulin release assay. Then, the generated IPCs were labeled with PKH26 dye prior to transplantation in experimental animals. Twenty-eight days later, blood glucose, serum insulin (INS), c-peptide (CP), and visfatin (VF) levels and pancreatic glucagon (GC) level were estimated. Pancreatic forkhead box protein A2 (Foxa2) and SRY-box transcription factor 17 (Sox17), insulin-like growth factor I (IGF-1), and fibroblast growth factor10 (FGF 10) gene expression levels were analyzed. Results Dental stem cells were successfully differentiated into IPCs that demonstrated increased expression of pancreatic endocrine genes. IPCs released insulin after being subjected to high levels of glucose. In vivo findings uncovered that the implanted IPCs triggered significant decrease in blood glucose, serum VF, and pancreatic GC levels with significant increase in serum INS and CP levels. Furthermore, the implanted IPCs provoked significant upregulation in the expression level of pancreatic genes. Histopathological description of the pancreas tissues revealed that transplantation of IPCs ameliorated the destabilization of pancreas tissue architecture. Conclusion This study demonstrates the significant role of the implantation of IPCs generated from dental-derived stem cells in treatment of diabetes mellitus. |
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issn | 2090-5920 |
language | English |
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publishDate | 2022-06-01 |
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series | Journal of Genetic Engineering and Biotechnology |
spelling | doaj.art-7ef83ae0126e4144b2e55e26764cb3362024-04-16T18:29:15ZengElsevierJournal of Genetic Engineering and Biotechnology2090-59202022-06-0120111510.1186/s43141-022-00369-6Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiationRiham M. Aly0Hadeer A. Aglan1Ghada Nour Eldeen2Nadia S. Mahmoud3Eman H. Aboul-Ezz4Hanaa H. Ahmed5Basic Dental Science Department, Oral Medicine & Dentistry Research Institute, National Research CentreStem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research CentreMolecular Genetics & Enzymology Department, Human Genetic & Genome Research Institute, National Research CentreStem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research CentreBasic Dental Science Department, Oral Medicine & Dentistry Research Institute, National Research CentreStem Cell Laboratory, Center of Excellence for Advanced Sciences, National Research CentreAbstract Background This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament and were induced to differentiate into insulin-producing cells (IPCs) using laminin-based differentiation protocol for 14 days. Confirmation of IPCs was performed through real-time PCR analysis and insulin release assay. Then, the generated IPCs were labeled with PKH26 dye prior to transplantation in experimental animals. Twenty-eight days later, blood glucose, serum insulin (INS), c-peptide (CP), and visfatin (VF) levels and pancreatic glucagon (GC) level were estimated. Pancreatic forkhead box protein A2 (Foxa2) and SRY-box transcription factor 17 (Sox17), insulin-like growth factor I (IGF-1), and fibroblast growth factor10 (FGF 10) gene expression levels were analyzed. Results Dental stem cells were successfully differentiated into IPCs that demonstrated increased expression of pancreatic endocrine genes. IPCs released insulin after being subjected to high levels of glucose. In vivo findings uncovered that the implanted IPCs triggered significant decrease in blood glucose, serum VF, and pancreatic GC levels with significant increase in serum INS and CP levels. Furthermore, the implanted IPCs provoked significant upregulation in the expression level of pancreatic genes. Histopathological description of the pancreas tissues revealed that transplantation of IPCs ameliorated the destabilization of pancreas tissue architecture. Conclusion This study demonstrates the significant role of the implantation of IPCs generated from dental-derived stem cells in treatment of diabetes mellitus.https://doi.org/10.1186/s43141-022-00369-6Dental stem cellsInsulin-producing cellsDiabetes mellitusLamininDifferentiation |
spellingShingle | Riham M. Aly Hadeer A. Aglan Ghada Nour Eldeen Nadia S. Mahmoud Eman H. Aboul-Ezz Hanaa H. Ahmed Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation Journal of Genetic Engineering and Biotechnology Dental stem cells Insulin-producing cells Diabetes mellitus Laminin Differentiation |
title | Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation |
title_full | Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation |
title_fullStr | Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation |
title_full_unstemmed | Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation |
title_short | Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation |
title_sort | efficient generation of functional pancreatic β cells from dental derived stem cells via laminin induced differentiation |
topic | Dental stem cells Insulin-producing cells Diabetes mellitus Laminin Differentiation |
url | https://doi.org/10.1186/s43141-022-00369-6 |
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