Mechanism study for hypoxia induced differentiation of insulin-producing cells from umbilical cord blood-derived mesenchymal stem cells

• Published in: Biochemical and biophysical research communications Vol. 466; no. 3; pp. 444 - 449
• Main Authors: Sun, Bo, Meng, Xian-Hui, Liu, Rui, Yan, Shancheng, Xiao, Zhong-Dang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-10-2015
• Subjects: c-Met; Cell Differentiation; Cell Hypoxia; Differentiation; Fetal Blood - cytology; Fetal Blood - metabolism; HGF; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxic; In Vitro Techniques; Infant, Newborn; Insulin - biosynthesis; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; RNA Interference; PBS; FGF; HIF; EGF; HGF; HGFR; KGF; UCB-MSCs; PVDF; BSA; DMEM; SD; IPCs; c-Met; Hypoxic; Differentiation; Mesenchymal stem cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.09.047

Recently, we have successfully obtained functional IPCs efficiently from umbilical cord blood-derived mesenchymal stem cells by using hypoxia treatment. In this study, we further elaborated that the improved function and viability of IPCs are the result of the interaction β cell development pathway and c-Met/HGF axis induced by hypoxia. We found that hypoxia induced c-MET elevation is efficiently initiated the early stage differentiation IPCs from MSCs, and HGF improved the fully differentiation of IPCs by inducing the expression of NGN3. This finding may contribute to understanding β cell development and the development of stem cell therapy for diabetes.
•Interaction β-cell development pathway and c-Met/HGF axis improved viability of IPCs.•Hypoxia induced c-MET initiated the early stage differentiation IPCs from MSCs.•HGF improved the fully differentiation of IPCs by inducing the expression of NGN3.