Coexpression of Pdx1 and betacellulin in mesenchymal stem cells could promote the differentiation of nestin-positive epithelium-like progenitors and pancreatic islet-like spheroids

• Published in: Stem cells and development Vol. 17; no. 4; p. 815
• Main Authors: Li, Lisha, Li, Furong, Qi, Hui, Feng, Gao, Yuan, Kehu, Deng, Hongkui, Zhou, Hanxin
• Format: Journal Article
• Language: English
• Published: United States 01.08.2008
• Subjects: Animals; Betacellulin; 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 Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nestin; Rats; Rats, Sprague-Dawley; Spheroids, Cellular - cytology; Spheroids, Cellular - metabolism; Trans-Activators - biosynthesis; Trans-Activators - genetics
• ISSN: 1557-8534
• DOI: 10.1089/scd.2008.0060

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.