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PMID:18439098

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Citation

Li, L, Li, F, Qi, H, Feng, G, Yuan, K, Deng, H and Zhou, H (2008) Coexpression of Pdx1 and betacellulin in mesenchymal stem cells could promote the differentiation of nestin-positive epithelium-like progenitors and pancreatic islet-like spheroids. Stem Cells Dev. 17:815-23

Abstract

Mesenchymal stem cells (MSCs) have already been proved to be multipotent. Our goal was to evaluate the differentiating ability of rat MSCs into insulin-secreting cells in vitro to cure diabetes resulting from abnormal function of pancreatic islets. MSCs were identified by Fluorescence-activated cell sorting (FACS). Pdx1 is a transcription factor involved in the early endocrine development. Betacellulin (BTC) is a growth factor involved in beta-cell maturation. MSCs were transfected with plasmids carrying rat Pdx1 and BTC genes. Coexpression of Pdx1 and BTC significantly increased the number of nestin-positive epithelium-like progenitors and islet-like spheroids which differentiated from MSCs. In Pdx1- and BTC-expressed (Pdx1+ + BTC+) MSCs, insulin and Glut-2 mRNA levels significantly rose. The number of islet-like cells was also evidently augmented. In response to glucose, Pdx1+ + BTC+ MSCs released insulin and C-peptide. It is concluded that genetic manipulation of transcription factor Pdx1 and growth factor BTC in combination with appropriate differentiating culture could induce MSCs into the pancreatic lineage in vitro and produce islet-like spheroids that could secrete increased levels of insulin in response to glucose.

Links

PubMed Online version:10.1089/scd.2008.0060

Keywords

Animals; Cell Differentiation/physiology; Cells, Cultured; Epithelium/metabolism; Gene Expression; Homeodomain Proteins/biosynthesis; Homeodomain Proteins/genetics; Insulin-Secreting Cells/cytology; Insulin-Secreting Cells/metabolism; Intercellular Signaling Peptides and Proteins/biosynthesis; Intercellular Signaling Peptides and Proteins/genetics; Intermediate Filament Proteins/biosynthesis; Intermediate Filament Proteins/genetics; Mesenchymal Stem Cells/cytology; Mesenchymal Stem Cells/metabolism; Nerve Tissue Proteins/biosynthesis; Nerve Tissue Proteins/genetics; Rats; Rats, Sprague-Dawley; Spheroids, Cellular/cytology; Spheroids, Cellular/metabolism; Trans-Activators/biosynthesis; Trans-Activators/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:Q9JJM4

involved_in

GO:0045597: positive regulation of cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:PDX1

involved_in

GO:0032024: positive regulation of insulin secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

SALTI:HLYE

GO:0016021: integral component of membrane

ECO:0000315:

C

Fig 1: the SARB collection shown to cause systemic infections in humans have SPI-18 and hlyE and express an active hemolysin revealed upon bacterial envelope destabilization.

complete
CACAO 10725


See also

References

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