scholarly journals Application of human iPS cell-derived vascular cell differentiation induction method to elucidation of vascular pathology

Impact ◽  
2021 ◽  
Vol 2021 (5) ◽  
pp. 16-18
Author(s):  
Daisuke Taura
Keyword(s):  
Endothelial Cells ◽  
Cell Differentiation ◽  
Animal Models ◽  
Vascular Endothelial Cells ◽  
Es Cells ◽  
Ips Cells ◽  
Vascular Endothelial ◽  
Vascular Cell ◽  
Mural Cells ◽  
Human Ips Cells

Cardiovascular diseases such as arteriosclerosis are a leading cause of death in developed countries. Various factors, including diet, exercise and genetics, can play a role in the onset of such conditions and the development of treatment options is complex and often involves the use of animal models. However, there are limitations with the use of animal models due to their inherent differences to humans, meaning that research results aren't always translatable. Associate Professor Daisuke Taura, Department of Diabetes, Endocrinology and Nutrition, Kyoto University, Japan, is interested in the use of in vitro techniques for investigating cardiovascular conditions. He is conducting vascular cell differentiation induction research using human embryonic stem cells (ES) cells and induced pluripotent cells (iPS), which can be induced to differentiate into any type of human cell, provided the right culturing conditions are present. In a world first, Taura successfully induced vascular constituent cells from human iPS cells, which led to important results in the establishment of vascular cells with autosomal dominant polycystic kidney disease (ADPKD) and moyamoya disease. Ultimately, Taura and his team are working towards a radical treatment for atherosclerotic diseases, and are also seeking to induce differentiation of vascular constituent cells using human ES/ iPS cells and explore their development and differentiation processes. Taura has been successful in improving on culture methods and, in doing so, achieved the differentiation of human ES cells into vascular endothelial cells and mural cells, and the differentiation of human iPS cells into vascular endothelial cells and mural cells.

VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B

2009 ◽  
Vol 297 (5) ◽  
pp. H1685-H1696 ◽  
Author(s):  
Mitsuho Onimaru ◽  
Yoshikazu Yonemitsu ◽  
Takaaki Fujii ◽  
Mitsugu Tanii ◽  
Toshiaki Nakano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Neutralizing Antibody ◽  
Vascular Endothelial ◽  
Mural Cell ◽  
Mural Cells ◽  
Type 3 ◽  
Endothelial Growth Factor ◽  
Capillary Stability

Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) using neutralizing antibody AFL-4 abrogated FGF-2-mediated limb salvage and blood flow recovery in severely ischemic hindlimb. Interestingly, inhibition of VEGFR3 activity not only diminished lymphangiogenesis, but induced marked dilatation of capillary vessels, showing mural cell dissociation. In these mice, VEGF-C and PDGF-B were upregulated in the later phase after induced ischemia, on day 7, when exogenous FGF-2 expression had already declined, and blockade of VEGFR3 or PDGF-BB activities diminished PDGF-B or VEGF-C expression, respectively. These results clearly indicate that VEGF-C is a critical mediator, not only for lymphangiogenesis, but also for capillary stabilization, the essential molecular mechanism of communication between endothelial cells and mural cells during neovascularization.

scholarly journals Hepatocyte growth factor mediates angiopoietin-induced smooth muscle cell recruitment

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1260-1266 ◽  
Author(s):  
Hanako Kobayashi ◽  
Laura M. DeBusk ◽  
Yael O. Babichev ◽  
Daniel J. Dumont ◽  
Pengnian Charles Lin
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Mural Cell ◽  
Mural Cells ◽  
Hepatocyte Growth ◽  
Vascular Maturation

Abstract Communication between endothelial cells (ECs) and mural cells is critical in vascular maturation. Genetic studies suggest that angiopoietin/Tie2 signaling may play a role in the recruitment of pericytes or smooth muscle cells (SMCs) during vascular maturation. However, the molecular mechanism is unclear. We used microarray technology to analyze genes regulated by angiopoietin-1 (Ang1), an agonist ligand for Tie2, in endothelial cells (ECs). We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation. We confirmed this finding by Northern blot and Western blot analyses in cultured vascular endothelial cells. Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay. Addition of a neutralizing anti-HGF antibody inhibited Ang1-induced SMC recruitment, indicating that the induction of SMC migration by Ang1 was caused by the increase of HGF. Interestingly, Ang2, an antagonist ligand of Tie2, inhibited Ang1-induced HGF production and Ang1-induced SMC migration. Finally, we showed that deletion of Tie2 in transgenic mouse reduced HGF production. Collectively, our data reveal a novel mechanism of Ang/Tie2 signaling in regulating vascular maturation and suggest that a delicate balance between Ang1 and Ang2 is critical in this process.

Vascular endothelial cell lineage-specific promoter in transgenic mice

Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1089-1098 ◽  
Author(s):  
T.M. Schlaeger ◽  
Y. Qin ◽  
Y. Fujiwara ◽  
J. Magram ◽  
T.N. Sato
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Es Cells ◽  
Vascular Endothelial Cell ◽  
Cell Lineage ◽  
Vascular Endothelial ◽  
Lacz Reporter

Vascular endothelial cells play essential roles in the function and development of the cardiovascular system. However, due to the lack of lineage-specific markers suitable for molecular and biochemical analyses, very little is known about the molecular mechanisms that regulate endothelial cell differentiation. We report the first vascular endothelial cell lineage-specific (including angioblastic precursor cells) 1.2 kb promoter in transgenic mice. Moreover, deletion analysis of this promoter region in transgenic embryos revealed multiple elements that are required for the maximum endothelial cell lineage-specific expression. This is a powerful molecular tool that will enable us to identify factors and cellular signals essential for the establishment of vascular endothelial cell lineage. It will also allow us to deliver genes specifically into this cell type in vivo to test specifically molecules that have been implicated in cardiovascular development. Furthermore, we have established embryonic stem (ES) cells from the blastocysts of the transgenic mouse that carry the 1.2 kb promoter-LacZ reporter transgene. These ES cells were able to differentiate in vitro to form cystic embryoid bodies (CEB) that contain endothelial cells determined by PECAM immunohistochemistry. However, these in vitro differentiated endothelial cells did not express the LacZ reporter gene. This indicates the lack of factors and/or cellular interactions which are required to induce the expression of the reporter gene mediated by this 1.2 kb promoter in this in vitro differentiation system. Thus this system will allow us to screen for the putative inducers that exist in vivo but not in vitro. These putative inducers are presumably important for in vivo differentiation of vascular endothelial cells.

scholarly journals Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Susov Dhakal ◽  
Shahar Rotem-Bamberger ◽  
Josilyn R. Sejd ◽  
Meyrav Sebbagh ◽  
Nathan Ronin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Endothelial Cell ◽  
Cell Differentiation ◽  
Gas Exchange ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Retinal Development ◽  
Vascular Endothelial ◽  
Vertebrate Eye

Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. The retinal phenotypes in these genetic systems were not identical, with endothelial cell-depleted retinas displaying laminar disorganization, cell death, reduced proliferation, and reduced cell differentiation. In contrast, the lack of blood flow resulted in a milder retinal phenotype showing reduced proliferation and reduced cell differentiation, indicating that an endothelial cell-derived factor(s) is/are required for laminar organization and cell survival. The lack of erythrocytes did not result in an obvious retinal phenotype, confirming that defects in retinal development that result from vascular manipulations are not due to poor gas exchange. These findings underscore the importance of the cardiovascular system supporting and controlling retinal development in ways other than supplying oxygen. In addition, these findings identify a key developmental window for these interactions and point to distinct functions for vascular endothelial cells vs. circulating factors.

Sign in / Sign up

Export Citation Format

Share Document