Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

El-Hattab, Mariam Y.; Nagumo, Yoshiaki; Gourronc, Françoise A.; Klingelhutz, Aloysius J.; Ankrum, James A.; Sander, Edward A.

doi:10.1038/s41598-020-67175-3

Cited by 15 publications

(19 citation statements)

References 82 publications

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“…RJCFs were embedded in fibrin gels at a cell density of 1 million cells/ml. Gels were produced as described previously ( Sander et al, 2011 ; El-Hattab et al, 2020 ) by combining cells with dissolved fibrinogen (F-8630, Sigma, St. Louis, MO), 20 mM HEPES buffered saline (H-0887, Sigma, St. Louis, MO), calcium chloride (Avantor, Center Valley, PA), and dissolved thrombin (T-4648, Sigma, St. Louis, MO). 2 ml of this solution were then added to the cavities of each bioreactor and allowed to polymerize at room temperature for 10 min before being transferred to the incubator for an additional 30 min of polymerization.…”

Section: Methodsmentioning

confidence: 99%

Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets

Scholp

Jensen

Chinnathambi

et al. 2022

Front. Bioeng. Biotechnol.

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Tissue fibrosis is a major health issue that impacts millions of people and is costly to treat. However, few effective anti-fibrotic treatments are available. Due to their central role in fibrotic tissue deposition, fibroblasts and myofibroblasts are the target of many therapeutic strategies centered primarily on either inducing apoptosis or blocking mechanical or biochemical stimulation that leads to excessive collagen production. Part of the development of these drugs for clinical use involves in vitro prescreening. 2D screens, however, are not ideal for discovering mechanobiologically significant compounds that impact functions like force generation and other cell activities related to tissue remodeling that are highly dependent on the conditions of the microenvironment. Thus, higher fidelity models are needed to better simulate in vivo conditions and relate drug activity to quantifiable functional outcomes. To provide guidance on effective drug dosing strategies for mechanoresponsive drugs, we describe a custom force-bioreactor that uses a fibroblast-seeded fibrin gels as a relatively simple mimic of the provisional matrix of a healing wound. As cells generate traction forces, the volume of the gel reduces, and a calibrated and embedded Nitinol wire deflects in proportion to the generated forces over the course of 6 days while overhead images of the gel are acquired hourly. This system is a useful in vitro tool for quantifying myofibroblast dose-dependent responses to candidate biomolecules, such as blebbistatin. Administration of 50 μM blebbistatin reliably reduced fibroblast force generation approximately 40% and lasted at least 40 h, which in turn resulted in qualitatively less collagen production as determined via fluorescent labeling of collagen.

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Section: Methodsmentioning

confidence: 99%

Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets

Scholp

Jensen

Chinnathambi

et al. 2022

Front. Bioeng. Biotechnol.

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“…Specifically, the α‐SMA phenotype of myofibroblasts was markedly reduced and did not induce adipogenic differentiation of hypertrophic scar or keloid fibroblasts. El‐Hattab et al 61 proposed that human adipocyte‐conditioned medium promotes fibroblast conversion to myofibroblast transformation. Therefore, more studies should be conducted to draw more definitive conclusions and more advances are required to understand the mechanisms underlying myofibroblast reprogramming.…”

Section: Therapeutic Potential Of Myofibroblast‐to‐adipocyte Reprogra...mentioning

confidence: 99%

Novel prospects for scarless wound healing: The roles of myofibroblasts and adipocytes

Teng

Zou

Zhou

et al. 2022

J Cellular Molecular Medi

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Disturbances or defects in the process of wound repair can disrupt the delicate balance of cells and molecules necessary for complete wound healing, thus leading to chronic wounds or fibrotic scars. Myofibroblasts are one of the most important cells involved in fibrotic scars, and reprogramming provides a potential avenue to increase myofibroblast clearance. Although myofibroblasts have long been recognized as terminally differentiated cells, recent studies have shown that myofibroblasts have the capacity to be reprogrammed into adipocytes. This review intends to summarize the potential of reprogramming myofibroblasts into adipocytes. We will discuss myofibroblast lineage tracing, as well as the known mechanisms underlying adipocyte regeneration from myofibroblasts. In addition, we investigated different changes in myofibroblast gene expression, transcriptional regulators, signalling pathways and epigenetic regulators during skin wound healing. In the future, myofibroblast reprogramming in wound healing will be better understood and appreciated, which may provide new ideas for the treatment of scarless wound healing.

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“…Furthermore, blocking adipogenesis using peroxisome proliferator-activated receptor gamma (PPARγ) inhibitors GW9662 and bisphenol A diglycidyl ether (BADGE) resulted in similarly disrupted repair [ 8 ]. Consistently, adipocyte spheroid-derived secretions are sufficient to activate dermal fibroblasts into myofibroblasts [ 90 ]. To temporally regulate WAT ablation and prevent insulin resistance that occurs in constitutive mouse models [ 91 ], Zhang et al utilized FAT-ATTAC mice, which undergo induced apoptosis of adipocytes through activation of caspase 8.…”

Section: Contribution Of Adipocytes To Inflammationmentioning

confidence: 99%

Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts

Cooper

Haas

Noonepalle

et al. 2021

IJMS

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Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.

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Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

Cited by 15 publications

References 82 publications

Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets

Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets

Novel prospects for scarless wound healing: The roles of myofibroblasts and adipocytes

Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts

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