Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

Wong, Rebecca S. Y.

doi:10.1155/2011/406182

Cited by 31 publications

(24 citation statements)

References 74 publications

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“…Therefore, it is possible that N2 and B27 play a role in trans-differentiation of mesenchymal cells into neurallike cells. Basic fibroblast growth factor (bFGF) has been shown to be useful in the differentiation of insulin-producing cells (Wong, 2011). bFGF was shown to be secreted by endocrine precursor cells and to work as a chemoattractant to play a role in cell aggregation (Hardikar et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Dang¹,

Bui²,

Pham³

et al. 2015

Biomed Res Ther

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Abstract-Diabetes mellitus is a high incidence disease that has increased rapidly in recent years. Many new therapies are being studied and developed in order to find an effective treatment. An ideal candidate is stem cell therapy. In this study, we investigated the differentiation of adipose derived stem cells (ADSCs) into pseudo-islets in defined medium in vitro, to produce large quantities of insulin-producing cells (IPCs) for transplantation. ADSCs isolated from adipose tissue were induced to differentiate into islet-like insulin-producing cell clusters in vitro by inducing medium DMEM/F12 containing nicotinamide, N2, B27, bFGF, and insulin-transferrin-selenite (ITS). Differentiated cells were analyzed for properties of IPCs, including storage of Zn 2+ by dithizone staining, insulin production by ELISA and immunochemistry, and beta cell-related gene expression by reverse transcriptase PCR. The results showed that after 2 weeks of differentiation, the ADSCs aggregated into cell clusters, and after 4 weeks they formed islets, 50-400 micrometers in diameter. These islet cells exhibited characteristics of pancreatic beta cells as they were positive for dithizone staining, expressed insulin in vitro and C-peptide in the cytoplasm, and expressed pancreatic beta cellspecific genes, including Pdx-1, NeuroD, and Ngn3. These results demonstrate that ADSCs can be used to produce a large number of functional islets for research as well as application.

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Section: Discussionmentioning

confidence: 99%

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Dang¹,

Bui²,

Pham³

et al. 2015

Biomed Res Ther

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“…Many protocols were tried to differentiate MSCs into insulin producing cells [30]. Cultures in media with high glucose content were a common feature.…”

Section: Experiments With Mscsmentioning

confidence: 99%

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

El‐Badri

Ghoneim

2013

Journal of Nucleic Acids

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Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs) therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

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“…To explore induction further, we supplemented the culture medium with additional molecules to improve their maturation: GLP‐1, exendin‐4, and betacellulin. GLP‐1 was incorporated at Stage 3 of our original protocol to promote IPC maturation, whereas exendin‐4 and betacellulin have been widely used to promote the maturation and differentiation of MSCs into functional pancreatic cells (Kumar et al, ; Li, Lam, Xu, Lam, & Chung, ; Wong, ).…”

Section: Resultsmentioning

confidence: 99%

“…Gene expression was examined at the end of the three-stage differentiation process and increased fold change of each gene calculated by direct comparison to undifferentiated H-/G-CMSCs/AMSCs. With endocrine progenitor markers, NEUROG3 and ILS1, expression was (Kumar et al, 2014;Li, Lam, Xu, Lam, & Chung, 2010;Wong, 2011). (Figure 4f).…”

Section: H-/g-cmsc-ipcs Exhibit Elevated Pancreatic Lineage and Matmentioning

confidence: 97%

Chorionic and amniotic placental membrane‐derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities

Chen

Forsyth

2019

J Tissue Eng Regen Med

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Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC‐based generation of functional insulin‐producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow‐derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy‐ and GDM‐CMSCs/AMSCs to long‐term high‐glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM‐CMSCs/AMSCs, of senescence/stress markers. Short‐term high‐glucose culture promoted pancreatic transcription factor expression when coupled to a 16‐day step‐wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon‐like peptide‐1 and other chemical components, generated functional IPCs from both Healthy‐ and GDM‐CMSCs. Healthy‐/GDM‐AMSCs displayed betacellulin‐sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM‐CMSCs possess comparable therapeutic potential with Healthy‐CMSCs and can be effectively reprogrammed into insulin‐secreting cells.

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Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

Cited by 31 publications

References 74 publications

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Production of islet-like insulin-producing cell clusters in vitro from adiposederived stem cells

Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

Chorionic and amniotic placental membrane‐derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities

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