Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic β-cell differentiation in human embryonic stem cells

Cho, Young Min; Lim, Jung Mee; Yoo, Dae Hoon; Kim, Jae Hyun; Chung, Sung Soo; Park, Sang Gyu; Kim, Tae Hyuk; Oh, Sun Kyung; Choi, Young Min; Moon, Shin Yong; Park, Kyong Soo; Lee, Hong Kyu

doi:10.1016/j.bbrc.2007.11.112

Cited by 59 publications

(49 citation statements)

References 29 publications

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“…A stem cell with proliferative ability may provide a valuable source of islet progenitor cells. Several studies have demonstrated that a progenitor/ stem cell population can be expanded in vitro to generate large numbers of islet progenitor cells [28][29][30] . However, the efficient and directed differentiation of these cells to an endocrinal pancreatic lineage has been difficult to achieve.…”

Section: Discussionmentioning

confidence: 99%

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

Niu

Xie

et al. 2008

Acta Pharmacol Sin

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Aim: To study the expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats. Methods: pCMV.Ins, an expression plasmid of the human insulin gene, was constructed. In total, 100 μg pCMV.Ins wrapped with chitosan nanoparticles (chitosan-pCMV.Ins) was transfected to NIH3T3 cells and diabetes rats through lavage and coloclysis, respectively. The transfected cells were grown in Dulbecco's modified Eagle's medium, containing G418, for 72 h after transfection. The clones were selected and continued to grow in G418 medium for 24 d. The expression of human insulin was detected by immunohistochemistry. Human insulin in the culture medium of transfected cells was measured. Fasting blood glucose and plasma human insulin of diabetic rats were measured for 5 d after transfection. RT-PCR and Western blotting were performed to confirm the expression of the human insulin gene in diabetic rats. Results: Approximately 10% of NIH3T3 cells transfected by chitosan-pCMV.Ins expressed human insulin. Human insulin in the culture medium of NIH3T3 cells transfected by chitosan-pCMV.Ins significantly increased compared with that of the control group (P<0.01). Fasting blood glucose levels of the lavage group and the coloclysis group decreased significantly in 5 d (P<0.01) in comparison, while plasma insulin levels were much higher (P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and the coloclysis groups. Conclusion: The human insulin gene can be transfected and expressed successfully by chitosanpCMV.Ins in NIH3T3 cells and diabetes rats, which indicates that chitosan is a promising, non-viral vector for gene expression.

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Section: Discussionmentioning

confidence: 99%

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

Niu

Xie

et al. 2008

Acta Pharmacol Sin

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“…D'Amour et al reported the induction of hESCs into endocrine cells by mimicking pancreatic organogenesis in vivo following a five-step differentiation process involving definitive endoderm (DE), gut-tube endoderm, pancreatic endoderm, endocrine precursor, and hormone-expressing endocrine cells [17]. Subsequently, many scientists attempted to develop much faster or more efficient processes in their cell systems [18][19][20][21][22]. For example, Zhang et al developed a four-step induction protocol and obtained nearly 25% insulin-producing cells from hESCs [19].…”

Section: Introductionmentioning

confidence: 99%

A Synthetic Peptide-Acrylate Surface for Production of Insulin-Producing Cells from Human Embryonic Stem Cells

Lin

Hung

Yang

et al. 2014

Stem Cells and Development

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Human embryonic stem cells (hESCs), due to their self-renewal capacity and pluripotency, have become a potential source of transplantable b-cells for the treatment of diabetes. However, it is imperative that the derived cells fulfill the criteria for clinical treatment. In this study, we replaced common Matrigel with a synthetic peptide-acrylate surface (Synthemax) to expand undifferentiated hESCs and direct their differentiation in a defined and serum-free medium. We confirmed that the cells still expressed pluripotent markers, had the ability to differentiate into three germ layers, and maintained a normal karyotype after 10 passages of subculture. Next, we reported an efficient protocol for deriving nearly 86% definitive endoderm cells from hESCs under serumfree conditions. Moreover, we were able to obtain insulin-producing cells within 21 days following a simple three-step protocol. The results of immunocytochemical and quantitative gene expression analysis showed that the efficiency of induction was not significantly different between the Synthemax surface and the Matrigelcoated surface. Thus, we provided a totally defined condition from hESC culture to insulin-producing cell differentiation, and the derived cells could be a therapeutic resource for diabetic patients in the future.

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“…Nicotinic amide combined with betacellulin promotes the differentiation from stem cells to β-cells. Furthermore, betacellulin has the ability of promoting the differentiation of β-cells and speeding up the formation of pancreatic cell clusters (19)(20)(21). In addition, nicotinamide promotes the differentiation of fetal pancreatic precursor cells and increases the amount of β-cells (22,23).…”

Section: Discussionmentioning

confidence: 99%

Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro

Wang²,

Gao³

et al. 2011

Int J Mol Med

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Abstract. Mesenchymal stem cells (MSCs) have significant advantages over other stem cell types, and greater potential for immediate clinical application. MSCs would be an interesting cellular source for treatment of type 1 diabetes. In this study, MSCs from human umbilical cord were differentiated into functional insulin-producing cells in vitro by introduction of the pancreatic and duodenal homeobox factor 1 (PDX1) and in the presence of induction factors. The expressions of cell surface antigens were detected by flow cytometry. After induction in an adipogenic medium or an osteogenic medium, the cells were observed by Oil Red O staining and alkaline phosphatase staining. Recombinant adenovirus carrying the PDX1 gene was constructed and MSCs were infected by the recombinant adenovirus, then treated with several inducing factors for differentiation into islet β-like cells. The expression of the genes and protein related to islet β-cells was detected by immunocytochemistry, RT-PCR and Western blot analysis. Insulin and C-peptide secretion were assayed. Our results show that the morphology and immunophenotype of MSCs from human umbilical cord were similar to those present in human bone marrow. The MSCs could be induced to differentiate into osteocytes and adipocytes. After induction by recombined adenovirus vector with induction factors, MSCs were aggregated and presented islet-like bodies. Dithizone staining of these cells was positive. The genes' expression related to islet β-cells was found. After induction, insulin and C-peptide secretion in the supernatant were significantly increased. In conclusion, our results demonstrated that PDX1 gene-modified human umbilical cord mesenchymal stem cells could be differentiated into insulin-producing cells in vitro.

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Betacellulin and nicotinamide sustain PDX1 expression and induce pancreatic β-cell differentiation in human embryonic stem cells

Cited by 59 publications

References 29 publications

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

A Synthetic Peptide-Acrylate Surface for Production of Insulin-Producing Cells from Human Embryonic Stem Cells

Differentiation of PDX1 gene-modified human umbilical cord mesenchymal stem cells into insulin-producing cells in vitro

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