A new organotypic model containing dermal-type macrophages

Bêchetoille, Nicolas; Vachon, Hortense; Gaydon, Amandine; Boher, Aurélie; Fontaine, Thomas; Schaeffer, Evelyne; Décossas, Marion; André-Frei, V.; Mueller, Christopher G.

doi:10.1111/j.1600-0625.2011.01383.x

Cited by 40 publications

(20 citation statements)

References 29 publications

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“…Since macrophages play an important role in tumor progression [15], we now extended this model by including macrophages. The inclusion of macrophages into dermal equivalents has been described before [29], yet their influence on malignant keratinocytes in tumor OTCs had not been characterized. Macrophages were incorporated into the dermal equivalent consisting of collagen-I alone or together with fibroblasts, and skin SCC cells were seeded on top of those dermal equivalent.…”

Section: Discussionmentioning

confidence: 99%

“…Demonstration that this model can be adapted for a human system further extends its applicability to study the activation of human macrophages in detail. Descriptions of organotypic co-cultures containing macrophages include description of dermal equivalents modeling healthy skin [29] and the culture of tissue explants containing macrophages for the testis [40], neuroretina [41], hippocampal slices [42], and tumor [4]. The organotypic tumor model described here, however, has the great advantage over the described models to be independent of the inter-individual differences that can be a problem in explants cultures and to allow incorporation of macrophages of different origin.…”

Section: Discussionmentioning

confidence: 99%

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Integrating Macrophages into Organotypic Co-Cultures: A 3D In Vitro Model to Study Tumor-Associated Macrophages

et al. 2012

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Tumor progression is controlled by signals from cellular and extra-cellular microenvironment including stromal cells and the extracellular matrix. Consequently, three-dimensional in vitro tumor models are essential to study the interaction of tumor cells with their microenvironment appropriately in a biologically relevant manner. We have previously used organotypic co-cultures to analyze the malignant growth of human squamous cell carcinoma (SCC) cell lines on a stromal equivalent in vitro. In this model, SCC cell lines are grown on a collagen-I gel containing fibroblasts. Since macrophages play a critical role in the progression of many tumor types, we now have expanded this model by integrating macrophages into the collagen gel of these organotypic tumor co-cultures. This model was established as a murine and a human system of skin SCCs. The effect of macrophages on tumor progression depends on their polarization. We demonstrate that macrophage polarization in organotypic co-cultures can be modulated towards and M1 or an M2 phenotype by adding recombinant IFN-γ and LPS or IL-4 respectively to the growth medium. IL-4 stimulation of macrophage-containing cultures resulted in enhanced tumor cell invasion evidenced by degradation of the basement membrane, enhanced collagenolytic activity and increased MMP-2 and MMP-9. Interestingly, extended co-culture with tumor cells for three weeks resulted in spontaneous M2 polarization of macrophages without IL-4 treatment. Thus, we demonstrate that macrophages can be successfully integrated into organotypic co-cultures of murine or human skin SCCs and that this model can be exploited to analyze macrophage activation towards a tumor supporting phenotype.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrating Macrophages into Organotypic Co-Cultures: A 3D In Vitro Model to Study Tumor-Associated Macrophages

et al. 2012

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“…Their presence is essential for proper wound healing and can actually be anti-inflammatory. The incorporation of potentially anti-inflammatory dermal substitutes has been successfully incorporated into scaffolds with dermal fibroblasts and retain their ability to produce anti-inflammatory cytokines in vitro [151]. However to our knowledge, no study has shown in vivo effects of incorporating macrophages into skin substitutes.…”

Section: Components Of a Skin Substitutementioning

confidence: 99%

Methodologies in creating skin substitutes

Nicholas

Jeschke

Amini-Nik

2016

Cell. Mol. Life Sci.

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The creation of skin substitutes has significantly decreased morbidity and mortality of skin wounds. Although there are still a number of disadvantages of currently available skin substitutes, there has been a significant decline in research advances over the past several years in improving these skin substitutes. Clinically most skin substitutes used are acellular and do not use growth factors to assist wound healing, key areas of potential in this field of research. This article discusses the five necessary attributes of an ideal skin substitute. It comprehensively discusses the three major basic components of currently available skin substitutes: scaffold materials, growth factors, and cells, comparing and contrasting what has been used so far. It then examines a variety of techniques in how to incorporate these basic components together to act as a guide for further research in the field to create cellular skin substitutes with clinically better results.

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“…For example, by adding normal or malignant melanocytes, one can study the mechanisms of epidermal pigmentation or melanoma progression (Eves et al ., 2000). Also, immune cells, such as macrophages, can be added into OCS scaffolds to study more complex in vivo -like epidermal-dermal-immune signaling interactions in in vitro settings (Bechetoille et al ., 2011). …”

Section: Organotypic Cultures In Epidermal Researchmentioning

confidence: 99%