Spontaneous fibroblast‐derived pericyte recruitment in a human tissue‐engineered angiogenesis model in vitro

Berthod, François; Symes, Julie; Tremblay, Nathalie; Medin, Jeffrey A.; Auger, François A.

doi:10.1002/jcp.22943

Cited by 36 publications

(28 citation statements)

References 41 publications

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“…Since there were no pericytes in our cultured conditions, this step was inferred by basement membrane formation around the CLS. Berthod et al 27 showed that the pericytes could derive from fibroblast in vitro , which encouraged us to investigate the same effect with our model. The CLSs in psoriatic skin models are more numerous, complex, branched, dense, and chaotic than in healthy substitutes.…”

Section: Discussionsupporting

confidence: 53%

Study of In Vitro Capillary-Like Structures in Psoriatic Skin Substitutes

Ayata

Bouhout

Auger

et al. 2014

BioResearch Open Access

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Angiogenesis is one of the important hallmarks of psoriasis. The extension of the superficial microvascular structure and activated pro-angiogenic mediators in psoriasis seem to be important factors involved in the pathology. According to the changes of superficial microvasculature in psoriatic lesions, anti-angiogenic treatment could be a promising therapeutic strategy for psoriasis. The aim of this study was to construct an in vitro vascularized psoriatic skin substitute for fundamental research. Psoriatic fibroblasts and keratinocytes were isolated from psoriatic plaque biopsies, while healthy fibroblasts and keratinocytes, as well as microvascular endothelial cells, were isolated from healthy skin biopsies of cosmetic breast surgery. Psoriatic and healthy skin substitutes with and without endothelial cells were produced using the self-assembly approach. Afterward the substitutes were examined by histology, immunofluorescence studies, and three-dimensional (3D) confocal microscopy. Histological analysis and immunofluorescence staining of specific markers for endothelial cells (von Willebrand, PECAM-1 [CD31], and VE-cadherin [CD144]) and basement membrane component (collagen IV) demonstrated that endothelial cells have the ability to form capillary-like tubes. Moreover, the 3D branched structure of the capillary-like structures and an eagle eye view of them were observed by confocal microscopy. Also the semiquantification of capillary-like tubes (CLTs) was carried out with a 3D eagle eye view of substitutes, and more CLTs were observed in psoriatic substitutes. These results suggest that it is possible to observe 3D capillary-like structures in the self-assembled psoriatic skin substitutes, which could become a good in vitro testing model for anti-angiogenic drug research, and facilitate the study of this complex pathology, which links angiogenesis to its development.

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Section: Discussionsupporting

confidence: 53%

Study of In Vitro Capillary-Like Structures in Psoriatic Skin Substitutes

Ayata

Bouhout

Auger

et al. 2014

BioResearch Open Access

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“…These cells are both NG2 + and PDGFR-β + (Fig. 1f), consistent with a pericyte phenotype1718. Once established, the vessels rapidly lay down a collagen IV-rich basement membrane (Fig.…”

Section: Resultsmentioning

confidence: 53%

3D microtumors in vitro supported by perfused vascular networks

Sobrino

Phan

Datta

et al. 2016

Sci Rep

332

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There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs in vitro. This “organs-on-chips” approach aims to capture key structural and physiological characteristics of the target tissue. Here we describe in vitro vascularized microtumors (VMTs). This “tumor-on-a-chip” platform incorporates human tumor and stromal cells that grow in a 3D extracellular matrix and that depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal and breast cancer cells grow vigorously in the platform and respond to standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms of action can also be distinguished, and we find that drugs targeting only VEGFRs (Apatinib and Vandetanib) are not effective, whereas drugs that target VEGFRs, PDGFR and Tie2 (Linifanib and Cabozantinib) do regress the vasculature. Tumors in the VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared to their surrounding stroma, many show a higher free/bound NADH ratio consistent with their known preference for aerobic glycolysis. The VMT platform provides a unique model for studying vascularized solid tumors in vitro.

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“…To better quantify the specific angiogenic potential of each neurotrophic factor, we investigated their effect on CLT formation in vitro using our well-characterized tissue-engineered model of angiogenesis. [30][31][32] We demonstrated a major increase in the number of CLT for all neurotrophic factors. Indeed, NGF, GDNF, and NT-3 induced a 40% to 80% increase in the number of CLT.…”

Section: Blais Et Almentioning

confidence: 74%

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-EngineeredIn VitroModel

Blais

Lévesque

Bellenfant

et al. 2013

Tissue Engineering Part A

Self Cite

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Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells. We demonstrated that these peptides are highly potent angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to 80% increase in the number of capillary-like tubes was observed after the addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of GDNF. This is the first characterization of the direct angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated directly through binding with the neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB, GFRa-1 and c-ret that were all expressed by human endothelial cells, while this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in normal skin, they might have the potential to greatly increase angiogenesis in pathological situations.

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Spontaneous fibroblast‐derived pericyte recruitment in a human tissue‐engineered angiogenesis model in vitro

Cited by 36 publications

References 41 publications

Study of In Vitro Capillary-Like Structures in Psoriatic Skin Substitutes

Study of In Vitro Capillary-Like Structures in Psoriatic Skin Substitutes

3D microtumors in vitro supported by perfused vascular networks

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-EngineeredIn VitroModel

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