Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

Pence, Jacquelyn C.; Clancy, Kathryn B. H.; Harley, Brendan A.C.

doi:10.1002/adbi.201700056

Cited by 11 publications

(9 citation statements)

References 83 publications

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“…The ability to study dynamic processes of endometrial angiogenesis would provide insight into endometrial function and vascular remodeling. Our lab [26,29], along with other labs [49,50] [1,3,51]. Here, we report endothelial networks formed within the hydrogel that had average branch lengths of approximately 70 μm.…”

Section: Discussionsupporting

confidence: 59%

“…Endothelial cell networks were formed using previously described techniques by encapsulating HUVECs and HESCs in GelMA hydrogels in 2:1 and 5:1 ratios (HUVEC:HESC) with a total cell density of 3 x 10 6 cells/mL [26,29]. Briefly, cells were resuspended in prepolymer solution, pipetted into Teflon molds, and polymerized under UV light.…”

Section: Huvec-hesc Co-culturesmentioning

confidence: 99%

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A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

Zambuto

Clancy

Harley

2019

Preprint

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As the lining of the uterus and site of blastocyst implantation, the endometrium is a dynamic tissue that undergoes rapid cycles of growth, breakdown, and remodeling each menstrual cycle.Significant vascular remodeling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodeling enhance blood flow to the embryo ahead of placentation. Insight into endometrial vascular remodeling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective for this study was to develop a tissue engineering platform to investigate processes of endometrial angiogenesis and trophoblast invasion in a 3D environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue. Further, the hydrogel supports the formation of stable endometrial endothelial cell networks and attachment of a stratified endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment, and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.

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Section: Discussionsupporting

confidence: 59%

Section: Huvec-hesc Co-culturesmentioning

confidence: 99%

A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

Zambuto

Clancy

Harley

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ability to study the dynamic processes of endometrial angiogenesis would provide insight into endometrial function and vascular remodelling. Our laboratory [27,30], along with other laboratories [50,51], has successfully created endothelial cell networks in gelatin hydrogels by co-culturing endothelial cells with stromal cells. Here, as an artificial endometrial perivascular niche, HUVECs and HESCs were encapsulated in 5 wt% GelMA hydrogels.…”

Section: Discussionmentioning

confidence: 99%

A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion

2019

Self Cite

View full text Add to dashboard Cite

The endometrium is the lining of the uterus and site of blastocyst implantation. Each menstrual cycle, the endometrium cycles through rapid phases of growth, remodelling and breakdown. Significant vascular remodelling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodelling enhance blood flow to the embryo ahead of placentation. Understanding the mechanisms of endometrial vascular remodelling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective of this study was to develop a tissue engineering platform to investigate the processes of endometrial angiogenesis and trophoblast invasion in a three-dimensional environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue, supports the formation of endometrial endothelial cell networks with human umbilical vein endothelial cells and human endometrial stromal cells as an artificial endometrial perivascular niche and the culture of an endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.

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“…145 Vascular function is modulated by systemic and local levels of sex hormones and inflammatory cues. 146,147 In vitro, cultures of endometrial stromal and epithelial cells in the presence of estrogen regulate angiogenesis, 148 and signals from flow-activated endothelial cells enhance hormone response in endometrial stromal cells. 145 Encouragingly, a fusion of tissue engineering and microfluidic cell culture technologies has spurred development of devices and protocols that could be applied to modeling adenomyosis lesions.…”

Section: Vascularization and Immune Interactionsmentioning

confidence: 99%

Physiomimetic Models of Adenomyosis

et al. 2020

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Adenomyosis remains an enigmatic disease in the clinical and research communities. The high prevalence, diversity of morphological and symptomatic presentations, array of potential etiological explanations, and variable response to existing interventions suggest that different subgroups of patients with distinguishable mechanistic drivers of disease may exist. These factors, combined with the weak links to genetic predisposition, make the entire spectrum of the human condition challenging to model in animals. Here, after an overview of current approaches, a vision for applying physiomimetic modeling to adenomyosis is presented. Physiomimetics combines a system's biology analysis of patient populations to generate hypotheses about mechanistic bases for stratification with in vitro patient avatars to test these hypotheses. A substantial foundation for three-dimensional (3D) tissue engineering of adenomyosis lesions exists in several disparate areas: epithelial organoid technology; synthetic biomaterials matrices for epithelial–stromal coculture; smooth muscle 3D tissue engineering; and microvascular tissue engineering. These approaches can potentially be combined with microfluidic platform technologies to model the lesion microenvironment and can potentially be coupled to other microorgan systems to examine systemic effects. In vitro patient-derived models are constructed to answer specific questions leading to target identification and validation in a manner that informs preclinical research and ultimately clinical trial design.

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Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

Cited by 11 publications

References 83 publications

A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion

Physiomimetic Models of Adenomyosis

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