Insulin producing cells generation by overexpression of miR-375 in adipose-derived mesenchymal stem cells from diabetic patients

Piran, Mehran; Enderami, Seyed Ehsan; Piran, Mehrdad; Sedeh, Hadis Soltani; Seyedjafari, Ehsan; Ardeshirylajimi, Abdolreza

doi:10.1016/j.biologicals.2016.12.004

Cited by 38 publications

(24 citation statements)

References 13 publications

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“…20 Regarding the fact that miRNAs play a potential role in the biological activity of cells such as cell proliferation, differentiation, apoptosis, drug resistance, invasion, and metastasis, they could be used as molecular therapy for cancer. [21][22][23] In the present study, we investigated the effect of the miR-579 overexpression in A-172 and U251 glioblastoma cell lines. The universal genetic features of these two cell lines are mutations in genes such as p14ARF, p16 (CDKN2A) and PTEN.…”

Section: Discussionmentioning

confidence: 99%

The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

Kalhori

Irani

Soleimani

et al. 2019

J of Cellular Biochemistry

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Glioblastoma multiform (GBM) is a type of aggressive brain cancer with limited success in standard treatment. MicroRNAs are one of the most beneficial tools for diagnosis, prognosis, and treatment of cancer. This study aimed to investigate the effect of miR‐579 on cellular behaviors and expression of PI3K/AKT signaling pathway in GBM cell lines. In the present study, miR‐579 was overexpressed in U251 and A‐172 cell lines by using lentil vector, and its effect on cellular behavior such as proliferation and migration was investigated by the cell cycle, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), Annexin V, colony formation, Transwell and wound healing assays. MiR‐579 predicted target genes (AKT1, Rheb, PDK1, and a few others) were also evaluated by real‐time polymerase chain reaction or luciferase assay and Western blot analysis. Our results represented that overexpression of miR‐579 could inhibit proliferation, migration, cell cycle and also promoted the apoptosis of GBM cell lines. The luciferase reporter assay showed miR‐579 directly targets the 3 UTR of mTOR, Rheb, and PDK1 and repressed their expressions. Furthermore, the Western blot analysis showed that miR‐579 could downregulate the AKT1 and Rheb protein expression. Overall, our findings propose that miR‐579 functions as a novel tumor suppressor gene in GBM by regulating the PI3K/AKT signaling pathway and may serve as a therapeutic target for clinical therapy of glioblastoma multiform.

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Section: Discussionmentioning

confidence: 99%

The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

Kalhori

Irani

Soleimani

et al. 2019

J of Cellular Biochemistry

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“…Recently, many studies have sought to use stem cells to produce pancreatic beta cells and focus on the production and expansion of these alternative sources [5][6][7][8]. Meanwhile, induced pluripotent stem cells (iPSCs), due to their high potential of self-renewability and differentiation as well as low immunogenicity, are an appropriate cell source for use in alternative therapies [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, numerous studies have tried to use cell-based therapy for T1DM [12,13]. To obtain the cells needed for cell therapy; these studies have used various methods, such as gene transfer and the use of differentiation medium for the differentiation of stem cells into beta cells [5,11]. These strategies are expensive and time consuming.…”

Section: Introductionmentioning

confidence: 99%

Generation of insulin-producing cells from human induced pluripotent stem cells on PLLA/PVA nanofiber scaffold

Enderami

Kehtari

Abazari

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Pancreatic tissue engineering as a therapeutic option for restoring and maintenance of damaged pancreas function has a special focus to using synthetic Scaffolds. This study was designed to evaluate pancreatic differentiation of human induced pluripotent stem cells (hiPSCs) on poly-L-lactic acid and polyvinyl alcohol (PLLA/PVA) scaffolds as 3 D matrix. During differentiation process, morphology of cells gradually changed and iPSCs derived insulin producing cells (iPSCs-IPCs) formed spherical shaped cell aggregation that was the typical shape of islets of pancreas. The highly efficient differentiation of iPSCs into a relatively homogeneous population of IPCs was shown by immunostaining. Real-time reverse transcription polymerase chain reaction (RT-PCR) results demonstrated that iPSCs-IPCs expressed pancreas-specific transcription factors (Pdx1, insulin, glucagon and Ngn3). The expressions of these transcription factors in PLLA/PVA scaffold were significantly higher than 2 D groups. Furthermore, we showed that concentration of insulin and C-peptide in PLLA/PVA scaffold and/or 2 D culture in response to various concentrations of glucose increased but the difference between them were not significant. Altogether the current results demonstrated that PLLA/PVA scaffold could provide the microenvironment that promotes the pancreatic differentiation of iPSCs, up-regulate pancreatic-specific transcription factors and improved metabolic activity.

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“…Due to high potential self-renewability and differentiation capacity, induced pluripotent stem cells (iPSCs) are considered as an appropriate cell source to be used in alternative therapies. These cells are capable to differentiate into insulin-producing cells (IPCs) either by gene transfer or culture in differentiation medium [6][7][8][9]. However, these strategies are facing low differentiation efficiency when cells are cultured on tissue culture dishes.…”

Section: Introductionmentioning

confidence: 99%

Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold

Mansour

Barati

Soleimani

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mellitus (T1DM), however, is limited by islet shortage. The aim of this study was to prepare a polyethersulfone (PES) nanofibrous scaffolds to evaluate the pancreatic differentiation of human induced pluripotent stem cells (hiPSCs). The differentiation process in tissue culture dishes and PES scaffolds was evaluated at mRNA and protein level by RT-qPCR and immunofluorescence assay, respectively. The functionality of differentiated cells was determined by insulin and C-peptide release in response to glucose challenges. The results of this study showed that cells cultured on PES nanofibrous scaffolds exhibit more pancreatic b-cell characteristics as they express more pancreatic tissue-specific genes and proteins. Furthermore, the immunoassay showed that differentiated cells in both culture plates and PES scaffolds groups are functional and secrete C-peptide and insulin in response to glucose challenges. Altogether, the results of this study demonstrated that PES nanofibrous scaffold could provide the microenvironment that promotes the differentiation of induced pluripotent stem cells (iPSCs) into insulin producing cells.

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Insulin producing cells generation by overexpression of miR-375 in adipose-derived mesenchymal stem cells from diabetic patients

Cited by 38 publications

References 13 publications

The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

The effect of miR‐579 on the PI3K/AKT pathway in human glioblastoma PTEN mutant cell lines

Generation of insulin-producing cells from human induced pluripotent stem cells on PLLA/PVA nanofiber scaffold

Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold

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