Multinucleated giant cells from fibroblast cultures

Holt, Derick G.; Grainger, David W.

doi:10.1016/j.biomaterials.2011.02.021

Cited by 32 publications

(29 citation statements)

References 46 publications

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“…This type of cells might represent a macrophage line with phagocytic properties, as previously reported (Grzesiak et al 2011). Giant cells are formed due to nuclear division without cytokinesis and are prone to changes in various pathologies, such as fibrosis, cancer, aging, and the foreign body response (Holt and Grainger 2011). A larger population of giant cells observed in our study of equine cultures cultivated with metamizole, compared to cultures exposed to tolfenamic acid, may indicate increased activity of COX-2, induced by an intensified pro-inflammatory immune response.…”

Section: Discussionsupporting

confidence: 62%

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

Nicpoń¹,

Siudzińska²,

Marędziak³

et al. 2015

Polish Journal of Veterinary Sciences

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The influences of NSAIDs (Nonsteroidal Anti-inflammatory Drugs) -non-selective metamizole and selectively-acting tolfenamic acid were estimated on morphology, ultrastructure, and cytophysiological activity of canine (Ca) and equine (Eq) adipose-derived mesenchymal stem cells (ASCs). The lowest concentration of metamizole (0.01 mg/mL) stimulated the viability and cytophysiological activity of Ca ASCs and did not affect cell morphology. Stimulated cells possessed a proper, fibroblastic shape, with large, eccentrically located nuclei. Similar effects to those observed in Ca ASCs were found in Eq cells treated with both drugs. Cells cultivated with the intermediate (0.1 mg/mL) doses of NSAIDs displayed proper cell morphology, whereas cells cultivated in intermediate dose (0.1 mg/mL) became more flattened. The highest concentrations (1 mg/mL) of both drugs resulted in a cytotoxic effect in Ca and Eq ASCs. Based on these results, we conclude that stimulation of Ca and Eq ASCs with metamizole as well as Eq ASCs with tolfenamic acid can lead to positive effects only when the lowest drug concentrations are applied. This study indicates a different cellular response of canine and equine ASCs treated with metamizole and tolfenamic acid. The obtained data might be potentially useful in the study of functionalized veterinary biomaterials.

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Section: Discussionsupporting

confidence: 62%

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

Nicpoń¹,

Siudzińska²,

Marędziak³

et al. 2015

Polish Journal of Veterinary Sciences

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“…Studies in both the biomaterials and wound healing literature have shown complex and reciprocal cell-cell crosstalk between macrophages and fibroblasts during the processes of healing and fibrosis [69-72]. In the context of the foreign body reaction, these interactions have been shown to result in increased expression of MCP-1 (a potent recruiter of macrophages and a mitogen for fibroblasts), the inhibition of macrophage secretion of cytokines, and the promotion of fibroblast production of cytokines, among others [71].…”

Section: Resultsmentioning

confidence: 99%

Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration

et al. 2017

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The present study tests the hypothesis that transient, early-stage shifts in macrophage polarization at the tissue-implant interface from a pro-inflammatory (M1) to an anti-inflammatory/regulatory (M2) phenotype mitigates the host inflammatory reaction against a non-degradable polypropylene mesh material and improves implant integration downstream. To address this hypothesis, a nanometer-thickness coating capable of releasing IL-4 (an M2 polarizing cytokine) from an implant surface at early stages of the host response has been developed. Results of XPS, ATR-FTIR and Alcian blue staining confirmed the presence of a uniform, conformal coating consisting of chitosan and dermatan sulfate. Immunolabeling showed uniform loading of IL-4 throughout the surface of the implant. ELISA assays revealed that the amount and release time of IL-4 from coated implants were tunable based upon the number of coating bilayers and that release followed a power law dependence profile. In-vitro macrophage culture assays showed that implants coated with IL-4 promoted polarization to an M2 phenotype, demonstrating maintenance of IL-4 bioactivity following processing and sterilization. Finally, in-vivo studies showed that mice with IL-4 coated implants had increased percentages of M2 macrophages and decreased percentages of M1 macrophages at the tissue-implant interface during early stages of the host response. These changes were correlated with diminished formation of fibrotic capsule surrounding the implant and improved tissue integration downstream. The results of this study demonstrate a versatile cytokine delivery system for shifting early-stage macrophage polarization at the tissue-implant interface of a non-degradable material and suggest that modulation of the innate immune reaction at early stages of the host response may represent a preferred strategy for promoting biomaterial integration and success.

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“…Conflicting, inconsistent data in the archival literature plague any consensus view regarding in vitro assessments of macrophage response to biomaterials [13, 14, 39]. We hypothesize that macrophage sourcing and their culture conditions, including time, contribute to highly variable macrophage responses reported for such studies.…”

Section: Discussionmentioning

confidence: 98%

Extended culture of macrophages from different sources and maturation results in a common M2 phenotype

Chamberlain

Holt-Casper

Gonzalez-Juarrero

et al. 2015

J Biomedical Materials Res

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Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely employed in short term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development towards an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign body response and encapsulation in vivo often elicit a shift towards an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized but has important implications to in vitro modeling of in vivo host response.

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Multinucleated giant cells from fibroblast cultures

Cited by 32 publications

References 46 publications

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration

Extended culture of macrophages from different sources and maturation results in a common M2 phenotype

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