Bone Marrow-Derived Mesenchymal Stem Cells Improve Rat Islet Graft Revascularization by Upregulating ISL1. (3rd April 2021)

• Record Type: Journal Article
• Authors: Wang, Ying; Wang, Jing-Wen; Li, Yang; Tian, Xiao-Hui; Feng, Xin-Shun; Zhang, Shu-Cong; Liu, Pei-Jun; Xue, Wu-Jun; Zheng, Jin; Ding, Xiao-Ming
• Is Part Of: Stem cells. Volume 39:Number 8(2021)
• Page Start: 1033
• Page End: 1048
• Publication Date: 2021-04-03
• Subjects: bone marrow-derived mesenchymal stem cells -- insulin gene enhancer binding protein-1 -- islet -- revascularization -- transplantation; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3378
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation. Abstract : This study demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) led to an increase in insulin gene enhancer binding protein-1 (ISL1) expression in islets and improved the vascular remodeling after islet transplantation in an animal model. Furthermore, the results demonstrate that ISL1 can directly regulate endogenous vascular endothelial growth factor A (VEGFA) production in islets. These data indicate that ISL1 could be the molecular mediator that led to the effects of BMSCs on islet revascularization.