scholarly journals Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Guo Qing-Song ◽  
Zhu Ming-Yan ◽  
Wang Lei ◽  
Fan Xiang-Jun ◽  
Lu Yu-Hua ◽  
...  

Aims. The goal of cell transcription for treatment of diabetes is to generate surrogateβ-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normalβ-cells.Methods. Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.Results. Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.Conclusions. These findings suggest major implications for cell replacement strategies in generation of surrogateβ-cells for the treatment of diabetes.

2013 ◽  
Vol 22 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Amani M. Ismail ◽  
Mona A. Abou-El-Mahasen ◽  
...  

2020 ◽  
Author(s):  
JINGLU WANG ◽  
Pengxiu Dai ◽  
Tong Zou ◽  
Yangou Lv ◽  
Wen Zhao ◽  
...  

Abstract Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, our study in the alternative source of islets from bone marrow mesenchymal stem cells appears to be important.Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage1”, “stage2” and “stage3”. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM–receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, somatostatin receptor 2, ribosomal protein S6 kinase A6, and vasoactive intestinal peptide, could act as a foundation for further research.Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of pancreas.


2014 ◽  
Vol 41 (7) ◽  
pp. 4783-4794 ◽  
Author(s):  
Arefeh Jafarian ◽  
Mohammad Taghikhani ◽  
Saeid Abroun ◽  
Zahra Pourpak ◽  
Amir Allahverdi ◽  
...  

2021 ◽  
Author(s):  
JINGLU WANG ◽  
Pengxiu Dai ◽  
Tong Zou ◽  
Yangou Lv ◽  
Wen Zhao ◽  
...  

Abstract Background Bone marrow mesenchymal stem cells are a potential resource for the clinical therapy of certain diseases. Canine, as a companion animal, living in the same space with human, is an ideal new model for human diseases research. Because of the high prevalence of diabetes, alternative transplantation islets resource (i.e. insulin producing cells) for diabetes treatment will be in urgent need, which makes our research on the transdifferentiation of Bone marrow mesenchymal stem cells into insulin producing cells become more important.Result In this study, we completed the transdifferentiation process and achieved the transcriptome profiling of five samples with two biological duplicates, namely, “BMSCs”, “islets”, “stage1”, “stage2” and “stage3”, and the latter three samples were achieved on the second, fifth and eighth day of induction. A total of 11,530 differentially expressed transcripts were revealed in the profiling data. The enrichment analysis of differentially expressed genes revealed several signaling pathways that are essential for regulating proliferation and transdifferentiation, including focal adhesion, ECM–receptor interaction, tight junction, protein digestion and absorption, and the Rap1 signaling pathway. Meanwhile, the obtained protein–protein interaction network and functional identification indicating involvement of three genes, SSTR2, RPS6KA6, and VIP could act as a foundation for further research.Conclusion In conclusion, to the best of our knowledge, this is the first survey of the transdifferentiation of canine BMSCs into insulin-producing cells according with the timeline using next-generation sequencing technology. The three key genes we pick out may regulate decisive genes during the development of transdifferentiation of insulin producing cells.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Engy A. Abdel-Rahman ◽  
Asmaa M. Reda ◽  
...  

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine.Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.


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