Development of a Three-Dimensional Adipose Tissue Model for Studying Embryonic Exposures to Obesogenic Chemicals

Wang, Rebecca Y; Abbott, Rosalyn D.; Zieba, Adam; Borowsky, Francis E.

doi:10.1007/s10439-016-1752-x

Cited by 24 publications

(20 citation statements)

References 32 publications

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“…That team then used the system to test BPA and BPS. The exposed stem cell tissues increased their expression of adipogenic genes and also accumulated triglycerides [38]. The last article from 2017 was an observational study of children aged between 10 and 13 years.…”

Section: Dietary Bps Exposure and Obesogenic Effects/metabolic Disordersmentioning

confidence: 99%

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

et al. 2020

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In recent years, bisphenol analogues such as bisphenol S (BPS) have come to replace bisphenol A in food packaging and food containers, since bisphenol A (BPA) has been shown to leach into food and water, causing numerous negative health effects. Unfortunately, little or no research was done to determine the safety of these BPA-free products before they were marketed to the public as a healthier alternative. The latest studies have shown that some of these bisphenol analogues may be even more harmful than the original BPA in some situations. This article used a literature survey to investigate the bisphenol analogue BPS and compare it to BPA and other analogues with regards to increased obesity, metabolic disorders, cancer, and reproductive defects; among others. It was found that BPS works via different pathways than does BPA while causing equivalent obesogenic effects, such as activating preadipocytes, and that BPS was correlated with metabolic disorders, such as gestational diabetes, that BPA was not correlated with. BPS was also shown to be more toxic to the reproductive system than BPA and was shown to hormonally promote certain breast cancers at the same rate as BPA. Therefore, a strong argument may be made to regulate BPS in exactly the same manner as BPA.

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Section: Dietary Bps Exposure and Obesogenic Effects/metabolic Disordersmentioning

confidence: 99%

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

et al. 2020

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show abstract

“…Perhaps due to BPA's shared structural homology with estrogen, it appears to be able to upregulate the expression of downstream targets, including peroxisome proliferator-activated receptor gamma (PPAR γ) and lipoprotein lipase (LPL), at least based on the results from in vitro experiments on rodents [65]. Recent studies have also demonstrated that the G protein-coupled receptor-30 (GPR-30), a transmembrane receptor structurally unrelated to the nuclear ERs, mediates the rapid actions of estrogens, as well as xenoestrogens such as BPA, modulating the activity of the ERK and AKT pathways, which are responsible for survival and cell death processes [66].…”

Section: Bisphenol Amentioning

confidence: 99%

“…In 2016, Leem and colleagues [82] conducted a study where they analyzed the effects of high BPA concentrations (250 μM, 500 μM for 18 h) on human bone marrow MSCs and found that BPA had a disturbing effect on β-catenin signaling via superoxide anion overload. In the same year, Wang and colleagues [66] developed a 3D model to study the action of BPA on human embryonic MSCs and compared these data with ASCs. They found that BPA did not induce adipogenesis in ASCs and furthermore did not have a significant effect on embryonic MSCs.…”

Section: Adipogenic Differentiationmentioning

confidence: 99%

Bisphenol a and mesenchymal stem cells: Recent insights

et al. 2018

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Mesenchymal stem cells (MSCs) are found in all adult mesenchymal tissues. They play a role in the maintenance of tissue homeostasis and repair by allowing renewal of the cellular stock. MSCs can be isolated from both human and animal sources. These cells are important in regenerative medicine and cell therapy, thus adipose tissue is a rich and promising source of these cells. Adipose-derived stem cells (ASCs) are often effective and safe, and have been used in preclinical and clinical studies for both autologous and allogeneic transplantation. The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs provides an important alternative therapeutic solution for the treatment of many diseases. However, it is necessary to have control of the cell manipulation process prior to their use. Exposure of humans to the endocrine disruptor bisphenol A (BPA) has been associated with increased weight and obesity, but the mechanisms by which BPA increases adipose tissue in humans remains to be determined. BPA has been classified as a potent endocrine-disrupting chemical that interferes with adipogenesis. Currently, few studies have reported the effect of BPA on the integrity and capacity for differentiation of MSCs. Thus, this review aims to present, for the first time, a current survey and a discussion of the effects of BPA action on MSCs.

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“…In that case, iPSC-derived skin cells will be an important alternative to address practical difficulties in obtaining multiple tissue types from the same donor 23,50,51 . In addition, considering that other skin components, such as hair follicles 52 , vasculature 24 and adipose tissue 53 also play a role in the regulation of immune reactions in the skin, these components can be included in future constructs using recently developed tissue engineering approaches by our group 21,24 and others 54 .…”

Section: Discussionmentioning

confidence: 99%

Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing

Shin

Abaci

Herron

et al. 2020

Sci Rep

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Drug screening studies for inflammatory skin diseases are currently performed using model systems that only partially recapitulate human diseased skin. Here, we developed a new strategy to incorporate T cells into human 3D skin constructs (HSCs), which enabled us to closely monitor and quantitate T cell responses. We found that the epidermis promotes the activation and infiltration of T cells into the skin, and provides a directional cue for their selective migration towards the epidermis. We established a psoriatic HSC (pHSC) by incorporating polarized Th1/Th17 cells or CCR6+CLA+ T cells derived from psoriasis patients into the constructs. These pHSCs showed a psoriatic epidermal phenotype and characteristic cytokine profiles, and responded to various classes of psoriasis drugs, highlighting the potential utility of our model as a drug screening platform. Taken together, we developed an advanced immunocompetent 3D skin model to investigate epidermal-T cell interactions and to understand the pathophysiology of inflammatory skin diseases in a human-relevant and patient-specific context.Skin is equipped with a complex immune system that involves various immune cell types, such as T cells, Langerhans cells, dermal dendritic cells, mast cells, and basophils, which secrete cytokines and chemokines to regulate immune responses both locally and systemically. Perturbations in this complex regulatory mechanism due to genetic and/or environmental factors contribute to the development of inflammatory skin diseases 1 . Therefore, understanding the skin immune system is essential to investigate the pathogenesis of inflammatory skin diseases and to discover and validate effective targets for treatment.Psoriasis affects 2-3% of the Western population 2,3 and is a chronic inflammatory skin disease with dysregulated keratinocyte proliferation 4 . In the pathogenesis of psoriasis, the interplay between keratinocytes and immune cells is important for the initiation, progression and persistence of the disease. Psoriatic keratinocytes recruit and activate plasmacytoid dendritic cells and neutrophils to initiate psoriasis 5-8 , and produce autoantigens, such as LL37 5-7 , ADAMTSL5 9 , and PLA2G4D 10 to activate T cells. Once T cells and DCs are recruited and activated, a cytokine niche is established including IFNs, IL-17, TNFα, and IL-22 11-13 . These cytokines not only alter epidermal proliferation and differentiation 12,13 , but also activate keratinocytes to release chemokines and chemoattractants, which induce further recruitment and infiltration of inflammatory cells into the skin 11 . Although this complex feedback loop between keratinocytes and immune cells is central in the pathogenesis of psoriasis, current in vitro models do not capture these cellular interactions, such as migration of the immune cells, highlighting the need for an advanced model that recapitulates the physiological and immunological complexity of the disease.Although there have been improvements in the efficacy of biologic therapies, therapeutic outcomes v...

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Development of a Three-Dimensional Adipose Tissue Model for Studying Embryonic Exposures to Obesogenic Chemicals

Cited by 24 publications

References 32 publications

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

Bisphenol S in Food Causes Hormonal and Obesogenic Effects Comparable to or Worse than Bisphenol A: A Literature Review

Bisphenol a and mesenchymal stem cells: Recent insights

Recapitulating T cell infiltration in 3D psoriatic skin models for patient-specific drug testing

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