Pancreatic islet transplantation still represents a promising therapeutic strategy for curative treatment of type 1 diabetes mellitus. However, a limited number of organ donors and insufficient vascularization with islet engraftment failure restrict the successful transfer of this approach into clinical practice. To overcome these problems, we herein introduce a novel strategy for the generation of prevascularized islet organoids by the fusion of pancreatic islet cells with functional native microvessels. These insulin‐secreting organoids exhibit a significantly higher angiogenic activity compared to freshly isolated islets, cultured islets, and non‐prevascularized islet organoids. This is caused by paracrine signaling between the β‐cells and the microvessels, mediated by insulin binding to its corresponding receptor on endothelial cells. In vivo , the prevascularized islet organoids are rapidly blood‐perfused after transplantation by the interconnection of their autochthonous microvasculature with surrounding blood vessels. As a consequence, a lower number of islet grafts are required to restore normoglycemia in diabetic mice. Thus, prevascularized islet organoids may be used to improve the success rates of clinical islet transplantation.

Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2. These regulatory factors crucially determine NG2-mediated cellular processes such as glial scar formation in the central nervous system (CNS) or tumor growth and metastasis. Therefore, they are potential targets for the establishment of novel NG2-based therapeutic strategies in the treatment of CNS injuries, cancer and other conditions of these types.

Somatostatin is a peptide hormone, which most commonly is produced by endocrine cells and the central nervous system. In mammals, somatostatin originates from pre-prosomatostatin and is processed to a shorter form, i.e., somatostatin-14, and a longer form, i.e., somatostatin-28. The two peptides repress growth hormone secretion and are involved in the regulation of glucagon and insulin synthesis in the pancreas. In recent years, the processing and secretion of somatostatin have been studied intensively. However, little attention has been paid to the regulatory mechanisms that control its expression. This review provides an up-to-date overview of these mechanisms. In particular, it focuses on the role of enhancers and silencers within the promoter region as well as on the binding of modulatory transcription factors to these elements. Moreover, it addresses extracellular factors, which trigger key signaling pathways, leading to an enhanced somatostatin expression in health and disease.

MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR‐191–5p (miR‐191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR‐191 mimic (miR‐191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR‐191m–transfected mouse aortic rings was significantly reduced when compared with controls. Transfection with miR‐191 inhibitor (miR‐191i) induced proangiogenic effects. The anti‐ and proangiogenic activities of miR191m and −191i were further demonstrated in vivo. Additional molecular biologic analyses revealed that miR‐191m activates NF‐kB signaling by up‐regulating the mRNA expression of p65. miR‐191 also increased the mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of metalloproteinase‐1 and reduced the expression of the proangiogenic factors eNOS and matrix metalloproteinase‐1 and −9. Blockade of NF‐kB activation with Bay 11–7082 reversed the antiangiogenic effects of miR‐191m. These findings indicate that miR‐191 effectively suppresses angiogenesis by activation of the NF‐kB signaling pathway.—Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. miR‐191 suppresses angiogenesis by activation of NF‐kB signaling. FASEB J . 31, 3321–3333 (2017). www.fasebj.org