Characterization of microvascular endothelial cells isolated from the dermis of adult mouse tails

Talavera-Adame, Dodanim; Ng, Tina T.; Gupta, Ankur; Kurtovic, Silvia; Wu, Guey-Shuang; Dafoe, Donald C.

doi:10.1016/j.mvr.2011.04.009

Cited by 15 publications

(16 citation statements)

References 51 publications

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“…We also reported that BMPs are expressed by mouse dermal microvascular ECs [11]. In the present work, we observed that EBs treated with a combination of rhBMP-2 and rhBMP-4 recapitulated the effects induced by EC-CM (Fig.…”

Section: Bmp-2/-4 Mimicked the Effects Of Ec-cm On The Enhancement Ofsupporting

confidence: 79%

“…Although many in vivo studies have demonstrated the critical role of ECs in differentiation, the ECderived factors involved are still under investigation [2]. It is known that ECs express factors involved in differentiation, such as fibroblast growth factor (FGF), bone morphogenetic proteins (BMPs) that belong to transforming growth factor b (TGF-b) superfamily, and jagged 1 that belongs to Notch family [10][11][12]. However, the role of other factors that might be involved is still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The effects induced by EC-CM were similar to those effects observed in EB vasculature after treatment with a combination of rhBMP-2 and rhBMP-4. We recently reported that these factors are produced by mouse dermal microvascular ECs (mDMECs) but not by EC from mouse EOMA indicated a differential marker expression between ECs [11]. In another work, it has been reported that BMPs play a crucial role in vascular development and pathophysiological processes [21].…”

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confidence: 99%

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Bone Morphogenetic Protein-2/-4 Upregulation Promoted by Endothelial Cells in Coculture Enhances Mouse Embryoid Body Differentiation

Talavera-Adame

Gupta²,

Kurtovic³

et al. 2013

Stem Cells and Development

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Endothelial cells (ECs) provide inductive signals for cell differentiation in vivo. However, it is unknown if these cells promote such differentiation in vitro and the signals involved. We investigated whether ECs are able to enhance the differentiation of the three germ layers and the underlying mechanisms. We established a coculture system of mouse embryoid bodies (EBs) and ECs. Then, we analyzed the expression of markers representative of the three germ layers, such as PDX-1, proinsulin, insulin1 (endoderm), nestin, neurofilament light (ectoderm), CD31, cardiotin, and cardiac troponin I (mesoderm) in EBs cultured alone (controls) or with ECs. A significant increase of these markers was observed in EBs cocultured with ECs compared to controls. The cocultured EBs also exhibited more robust vascular networks similar to those EBs treated with bone morphogenetic protein-2 or -4 (BMP-2 or -4). Therefore, the role of these peptides in the differentiation was investigated. We found a significant upregulation of BMP-2/-4 and BMP receptor 1A in EBs treated with EC conditioned medium (EC-CM) at early or middle stages of EB development. Recombinant human BMP-2 and BMP-4 exerted similar effects than EC-CM in the expression of BMPs or in the upregulation of the three germ layer specific markers. BMP-2/-4 antagonists, such as noggin and chordinlike-1, respectively inhibited the EC-CM inductive effects. These results demonstrate that ECs enhance the differentiation in vitro of cells that derived from the three germ layers and that BMP-2/-4 play a central role in this process.

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Section: Bmp-2/-4 Mimicked the Effects Of Ec-cm On The Enhancement Ofsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Bone Morphogenetic Protein-2/-4 Upregulation Promoted by Endothelial Cells in Coculture Enhances Mouse Embryoid Body Differentiation

Talavera-Adame

Gupta²,

Kurtovic³

et al. 2013

Stem Cells and Development

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“…ECs play a key role in organogenesis [8, 13, 15–18]; after induction from the notochord, pancreatic bud cells interact with ECs from the aorta and the dorsal vein to induce the formation of pancreas progenitors [13, 14, 19]. Aortic ECs are crucial for the survival of the pancreatic mesenchyme, including Islet-1 + cells, which signal to induce the expression of PDX1, a master regulator of pancreatic organogenesis [20].…”

Section: Introductionmentioning

confidence: 99%

Effective endothelial cell and human pluripotent stem cell interactions generate functional insulin-producing beta cells

et al. 2016

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Aims/hypothesisEndothelial cells (ECs) play an essential role in pancreatic organogenesis. We hypothesise that effective in vitro interactions between human microvascular endothelial cells (HMECs) and human pluripotent stem cells (hPSCs) results in the generation of functional pancreatic beta cells.MethodsEmbryoid bodies (EBs) derived from hPSCs were cultured alone (controls) or with ECs in collagen gels. Subsequently, cells were analysed for pancreatic beta cell markers, and then isolated and expanded. Insulin secretion in response to glucose was evaluated in vitro by static and dynamic (perifusion) assays, and in vivo by EB transplantation into immunodeficient mice.ResultsCo-cultured EBs had a higher expression of mature beta cells markers and enhanced insulin secretion in vitro, compared with controls. In mice, transplanted EBs had higher levels of human C-peptide secretion with a significant reduction in hyperglycaemia after the selective destruction of native pancreatic beta cells. In addition, there was significant in vitro upregulation of bone morphogenetic proteins 2 and 4 (BMP-2, 4) in co-cultured cells, compared with controls.Conclusions/interpretationECs provide essential signalling in vitro, such as activation of the BMP pathway, for derivation of functional insulin-producing beta cells from hPSCs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-4078-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…The role of BMPs in pancreas development has also been explored previously [72,93] . We demonstrated that HMECs or mouse dermis as well as mouse AECs expressed BMPs and that BMP-2 and BMP-4 increased the phosphorylation levels of SMAD1,5,8 in pancreatic progenitors and beta-like cells derived from mouse ESCs [52,53,94] . These findings together with previous works pointed out the important role of ECs in beta-cell differentiation in vitro.…”

Section: Endothelium and Beta-cell Regeneration In Vivo And In Vitromentioning

confidence: 90%

Endothelium-derived essential signals involved in pancreas organogenesis

Talavera-Adame

Dafoe

2015

WJEM

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Endothelial cells (ECs) are essential for pancreas differentiation, endocrine specification, and endocrine function. They are also involved in the physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development such as pancreatic and duodenal homeobox-1. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. Endocrine precursors proliferate interspersed with ductal cells and exocrine precursors and, at some point of development, these endocrine precursors migrate to pancreatic mesenchyme and start forming the islets of Langerhans. By the end of the gestation and close to birth, these islets contain immature beta cells with the capacity to express vascular endothelial growth factor and therefore to recruit ECs from the surrounding microenvironment. ECs in turn produce factors that are essential to maintain insulin secretion in pancreatic beta cells. Once assembled, a cross talk between endocrine cells and ECs maintain the integrity of islets toward an adequate function during the whole life of the adult individual. This review will focus in the EC role in the differentiation and maturation of pancreatic beta cells during embryogenesis as well as the current knowledge about the involvement of endothelium to derive pancreatic beta cells in vitro from mouse or human pluripotent stem cells.

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Characterization of microvascular endothelial cells isolated from the dermis of adult mouse tails

Cited by 15 publications

References 51 publications

Bone Morphogenetic Protein-2/-4 Upregulation Promoted by Endothelial Cells in Coculture Enhances Mouse Embryoid Body Differentiation

Bone Morphogenetic Protein-2/-4 Upregulation Promoted by Endothelial Cells in Coculture Enhances Mouse Embryoid Body Differentiation

Effective endothelial cell and human pluripotent stem cell interactions generate functional insulin-producing beta cells

Endothelium-derived essential signals involved in pancreas organogenesis

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