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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Main Authors: Riham M. Aly, Hadeer A. Aglan, Ghada Nour Eldeen, Nadia S. Mahmoud, Eman H. Aboul-Ezz, Hanaa H. Ahmed
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:Journal of Genetic Engineering and Biotechnology
Subjects:
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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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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