Human Papillary and Reticular Fibroblasts Show Distinct Functions on Tumor Behavior in 3D-Organotypic Cultures Mimicking Melanoma and HNSCC

Wu, Shidi; Rietveld, Marion; Hogervorst, M.; Gruijl, Frank de; Burg, Sjoerd H. van der; Vermeer, Maarten H.; Doorn, Remco van; Welters, Marij J.P.; Ghalbzouri, Abdoelwaheb El

doi:10.3390/ijms231911651

Cited by 5 publications

(7 citation statements)

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“…They can be roughly divided into those found in the papillary and the reticular dermis respectively, and these each show distinct expression patterns and functions 103 . Use of human dermal fibroblasts (HDFs) from either the papillary or reticular dermis did impact tumour invasion in melanoma and cutaneous squamous cell carcinoma (cSCC) 3D‐organotypic culture models 104 . Further, Narzt et al were able to show that the intracellular epilipidome of HDFs isolated from the reticular dermis showed elevated levels of oxidised phospholipids similar to in vitro generated replicative senescent or stress‐induced premature senescent (SIPS) fibroblasts 105 .…”

Section: Methods To Develop Human Skin Equivalentsmentioning

confidence: 99%

“…103 Use of human dermal fibroblasts (HDFs) from either the papillary or reticular dermis did impact tumour invasion in melanoma and cutaneous squamous cell carcinoma (cSCC) 3D-organotypic culture models. 104 Further, Narzt et al were able to show that the intracellular epilipidome of HDFs isolated from the reticular dermis showed elevated levels of oxidised phospholipids similar to in vitro generated replicative senescent or stress-induced premature senescent (SIPS) fibroblasts. 105 Finally, Weinmüllner et al reported that HSEs generated with SIPS-HDFs showed reduced epidermal thickness and compromised barrier function.…”

Section: Isolation Of Primary Human Fibroblastsmentioning

confidence: 98%

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Requisite instruments for the establishment of three‐dimensional epidermal human skin equivalents—A methods review

Czyz,

Kunth,

Gruber

et al. 2023

Experimental Dermatology

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Human skin equivalents (HSEs) are three‐dimensional skin organ culture models raised in vitro. This review gives an overview of common techniques for setting up HSEs. The HSE consists of an artificial dermis and epidermis. 3T3‐J2 murine fibroblasts, purchased human fibroblasts or freshly isolated and cultured fibroblasts, together with other components, for example, collagen type I, are used to build the scaffold. Freshly isolated and cultured keratinocytes are seeded on top. It is possible to add other cell types, for example, melanocytes, to the HSE—depending on the research question. After several days and further steps, the 3D skin can be harvested. Additionally, we show possible markers and techniques for evaluation of artificial skin. Furthermore, we provide a comparison of HSEs to human skin organ culture, a model which employs human donor skin. We outline advantages and limitations of both models and discuss future perspectives in using HSEs.

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Section: Methods To Develop Human Skin Equivalentsmentioning

confidence: 99%

Section: Isolation Of Primary Human Fibroblastsmentioning

confidence: 98%

Requisite instruments for the establishment of three‐dimensional epidermal human skin equivalents—A methods review

Czyz,

Kunth,

Gruber

et al. 2023

Experimental Dermatology

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“…Dermal equivalents were generated as described earlier (Wu et al , 2022 ). In short, 1 ml of cell‐free collagen (1 mg/ml) solution was pipetted into a six‐well‐filter insert (Corning Life Sciences, Tewksbury, MA).…”

Section: Methodsmentioning

confidence: 99%

Trichothiodystrophy‐associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation

Theil,

Pines,

Kalayci

et al. 2023

EMBO Mol Med

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The brittle hair syndrome Trichothiodystrophy (TTD) is characterized by variable clinical features, including photosensitivity, ichthyosis, growth retardation, microcephaly, intellectual disability, hypogonadism, and anaemia. TTD‐associated mutations typically cause unstable mutant proteins involved in various steps of gene expression, severely reducing steady‐state mutant protein levels. However, to date, no such link to instability of gene‐expression factors for TTD‐associated mutations in MPLKIP/TTDN1 has been established. Here, we present seven additional TTD individuals with MPLKIP mutations from five consanguineous families, with a newly identified MPLKIP variant in one family. By mass spectrometry‐based interaction proteomics, we demonstrate that MPLKIP interacts with core splicing factors and the lariat debranching protein DBR1. MPLKIP‐deficient primary fibroblasts have reduced steady‐state DBR1 protein levels. Using Human Skin Equivalents (HSEs), we observed impaired keratinocyte differentiation associated with compromised splicing and eventually, an imbalanced proteome affecting skin development and, interestingly, also the immune system. Our data show that MPLKIP, through its DBR1 stabilizing role, is implicated in mRNA splicing, which is of particular importance in highly differentiated tissue.

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“…In a similar manner, further investigation into dermal fibroblasts' heterogeneity based on scRNA-seq datasets has led to the characterization of two different subtypes of dermal fibroblasts, which are then divided into papillary dermal fibroblasts and reticular dermal fibroblasts subtypes in both mouse and human species [28,29] (Figure 1). Papillary and reticular fibroblasts show distinct morphology, functions, and gene expression profiles [29]. Papillary fibroblasts typically exhibit a more elongated and spindle-shaped appearance and are in the superficial layer of the dermis, known as the papillary dermis.…”

Section: Tissue Specificity and Heterogeneitymentioning

confidence: 99%

“…Reticular fibroblasts are primarily involved in synthesizing and maintaining the structural components of the dermal extracellular matrix [8,30]. Differences identified by Driskell et al [28] in papillary and reticular murine dermal fibroblasts gene expression profiles, reflect their specialized roles and location within the dermis [28,29]. Murine papillary dermal fibroblasts studied were shown to express higher levels of genes involved in the crosstalk between the epidermis and the papillary dermis and contribute to the maintenance of epidermal integrity, such as keratinocyte growth factor or fibroblast growth factor (fgf)-7 [30] and cell adhesion molecules like alpha-8 integrin (Itga8) [8].…”

Section: Tissue Specificity and Heterogeneitymentioning

confidence: 99%

Fibroblasts in Diabetic Foot Ulcers

Voza,

Huerta,

et al. 2024

IJMS

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Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These cells were previously considered to be “passive cells”, solely responsible for ensuring the turnover of the extracellular matrix (ECM). However, their versatility, including their ability to switch phenotypes in response to tissue injury and dynamic activity in the maintenance of tissue specific homeostasis and integrity have been recently revealed by the innovation of technological tools such as genetically modified mouse models and single cell analysis. These highly plastic and heterogeneous cells equipped with multifaceted functions including the regulation of angiogenesis, inflammation as well as their innate stemness characteristics, play a central role in the delicately regulated process of wound healing. Fibroblast dysregulation underlies many chronic conditions, including cardiovascular diseases, cancer, inflammatory diseases, and diabetes mellitus (DM), which represent the current major causes of morbidity and mortality worldwide. Diabetic foot ulcer (DFU), one of the most severe complications of DM affects 40 to 60 million people. Chronic non-healing DFU wounds expose patients to substantial sequelae including infections, gangrene, amputation, and death. A complete understanding of the pathophysiology of DFU and targeting pathways involved in the dysregulation of fibroblasts are required for the development of innovative new therapeutic treatments, critically needed for these patients.

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Human Papillary and Reticular Fibroblasts Show Distinct Functions on Tumor Behavior in 3D-Organotypic Cultures Mimicking Melanoma and HNSCC

Cited by 5 publications

References 57 publications

Requisite instruments for the establishment of three‐dimensional epidermal human skin equivalents—A methods review

Requisite instruments for the establishment of three‐dimensional epidermal human skin equivalents—A methods review

Trichothiodystrophy‐associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation

Fibroblasts in Diabetic Foot Ulcers

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