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Trans-differential Induction of Bovine (Bos taurus) Muscle Satellite Cells into Pancreatic Cells |
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Abstract Muscle satellite cells are potential myogenic cells capable of self-renewal and with potential multi-directional differentiation. Under normal circumstances, these cells are in resting state, but they can proliferate, differentiate and integrate into myotubes and form muscle cells. However, in vivo, these mesoderm originated satellite cells can not trans-differentiate into endoderm-derived insulin-producing cells. In this study, a muscle satellite cell line was isolated, cultured, identified and established from a bovine (Bos taurus) fetal muscle tissues. The muscle satellite cells were then induced to differentiate into insulin-producing cells. During pancreatic induction process, the genes associated with pancreatic development such as pancreatic and duodenal homeobox 1 (PDX1), neurogenin 3 (NGN3), Amylase and Insulin (INS) were analyzed. PDX1, an important transcription factor in differentiation of pancreatic islets, started to express after induction 2 d, reached to the highest level after 3 d, and kept lowest level after 4 d. NGN3 was an important transcription factor in the formation of endocrine cells, and was a key gene that controlled insulin secretion to extracellular, which the mRNA started to express after induction 3 d, reached to the highest level after 4 d and then declined. As a pancreatic extracellular secretion associated gene, Amylase mRNA appeared after 6 d and reached to the maximum after 8 d. INS expressed from 1st day and reached to the maximum at 11~12 d. Enzyme-linked immunosorbent assay (ELISA) of the culture media showed that the concentration of insulin secreted by the cultured cells reached to the maximum at 11~12 d. The insulin secretion was significantly increased in the glucose added culture medium, and glucose concentration regulated insulin secretion in the cultured cells, which was similar to adult islet fuction. In conclusion, the bovine muscle satellite cells could be trans-differentiated into pancreatic cells, and make response to glucose stimulation. The study provides basic data for further research and clinical application.
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Received: 13 July 2015
Published: 29 December 2015
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