Cellular and Molecular Dynamics in the Foreign Body Reaction

Luttikhuizen, Daniël T.; Harmsen, Martin C.; Luyn, Marja J. A. van

doi:10.1089/ten.2006.12.ft-126

Cited by 53 publications

(65 citation statements)

References 161 publications

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“…All three groups exhibited a relatively mild macrophagic reaction, and most of the macrophages were concentrated along the interface of the hydrogel remnants. It is this inflammatory response and hydrogel clearance-usually in combination with the secretion of cytokines and growth factors-that leads to functional tissue regeneration (44)(45)(46). These observations were also in agreement with our previous studies using PF plugs in a bone segmental defect model as well as with injectable PF hydrogels in a cardiac myocardial infarction model (47,48).…”

Section: Significancesupporting

confidence: 91%

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Therapies that promote angiogenesis have been successfully applied using various combinations of proangiogenic factors together with a biodegradable delivery vehicle. In this study we used bimodal noninvasive monitoring to show that the host response to a proangiogenic biomaterial can be drastically affected by the mode of implantation and the surface area-to-volume ratio of the implant material. Fluorescence/MRI probes were covalently conjugated to VEGF-bearing biodegradable PEG-fibrinogen hydrogel implants and used to document the in vivo degradation and liberation of bioactive constituents in an s.c. rat implantation model. The hydrogel biodegradation and angiogenic host response with three types of VEGFbearing implant configurations were compared: preformed cylindrical plugs, preformed injectable microbeads, and hydrogel precursor, injected and polymerized in situ. Although all three were made with identical amounts of precursor constituents, the MRI data revealed that in situ polymerized hydrogels were fully degraded within 2 wk; microbead degradation was more moderate, and plugs degraded significantly more slowly than the other configurations. The presence of hydrogel degradation products containing the fluorescent label in the surrounding tissues revealed a distinct biphasic release profile for each type of implant configuration. The purported in vivo VEGF release profile from the microbeads resulted in highly vascularized s.c. tissue containing up to 16-fold more capillaries in comparison with controls. These findings demonstrate that the configuration of an implant can play an important role not only in the degradation and resorption properties of the materials, but also in consequent host angiogenic response.biomaterial scaffold | angiogenesis | hydrogel | contrast agents | tissue regeneration W ith progress in the field of regenerative medicine relying more on approaches that deliver cells and/or bioactive factors using minimally invasive procedures, functional donor-tohost integration remains a critical challenge. In this context, biodegradable hydrogel scaffolds provide certain advantages, such as excellent tissue compatibility, temporary protection from host inflammation, and controlled resorption based on cell-mediated degradation (1). Effective transport properties to and within an implanted hydrogel are critical in the design of cell-seeded scaffolds, where the delivery of nutrients and removal of waste products from regions deep within the implant can severely limit the use of a patch for only the smallest of grafts (i.e., <0.5 mm) (2-4). Therefore, a great deal of research in the field of regenerative medicine has been devoted to ameliorate the survival of the cells and tissues with implants that use proangiogenic factors.One strategy is to enhance the localized formation of vascularized networks to improve the perfusion of oxygen and nutrients to the intended region in the body (2, 4, 5). This process is regulated by a number of different growth factors that stimulate a complex angiogenic res...

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Section: Significancesupporting

confidence: 91%

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Berdichevski

Yameen

Dafni³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…33 In addition, reduced expression of MMP-9 in MCP-1-null macrophages can be restored by addition of TNF-␣, an acute-phase proinflammatory cytokine with a role in the foreign body response that has received little attention. 6,34 TNF-␣ also induces apoptosis in macrophages adherent to biomaterials, and IL-4 inhibits the apoptosisinducing abilities of TNF-␣. 21,35 More relevant to this study, Robinson et al 36 demonstrated that in the monocytic cell line THP-1 and in human peripheral blood monocytes, addition of rMCP-1 stimulated TNF-␣ expression, which in turn induced MMP-9 release.…”

Section: Discussionmentioning

confidence: 99%

“…This suggestion is consistent with studies that demonstrated that anatomical site can greatly affect the host response to implanted materials. 6,19 FBGC formation was reduced in MCP-1-null mice and led to delayed biomaterial degradation. 11 Subsequent fusion experiments demonstrated that MCP-1-null macrophages are compromised in fusion because of inability to undergo cytoskeletal remodeling and induce MMP-9 in response to IL-4.…”

mentioning

confidence: 98%

Lack of TNF-α–Induced MMP-9 Production and Abnormal E-Cadherin Redistribution Associated with Compromised Fusion in MCP-1–Null Macrophages

Skokos

Charokopos

Khan

et al. 2011

The American Journal of Pathology

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Homotypic cell fusion occurs in several cell types including macrophages in the formation of foreign body giant cells. Previously, monocyte chemoattractant protein-1 (MCP-1) was demonstrated to be required for foreign body giant cell formation in the foreign body response. The present study investigated the fusion defect in MCP-1-null macrophages by implanting biomaterials intraperitoneally in wildtype and MCP-1-null mice and monitoring the macrophage response at 12 hours to 4 weeks. MCP-1-null mice exhibited reduced accumulation and fusion of macrophages on implants, which was associated with attenuation of the foreign body response. Consistent with previous in vitro findings, the level of matrix metalloproteinase-9 (MMP-9) was reduced in MCP-1-null macrophages adherent to implants. In contrast, CCR2 expression was unaffected. In vitro studies revealed reduced tumor necrosis factor-␣ (TNF-␣) production and abnormal subcellular redistribution of E-cadherin and ␤-catenin during fusion in MCP-1-null macrophages. Exogenous TNF-␣ caused an increase in the production of MMP-9 and rescued the fusion defect. Addition of GM6001 (MMP inhibitor) or NSC23766 (Rac1 inhibitor) indicated two distinct induction pathways, one for E-cadherin/␤-catenin and one for MCP-1, TNF-␣, and MMP-9. Considered together, these observations demonstrate that induction of E-cadherin/␤-catenin is not sufficient for fusion in the absence of MCP-1 or the downstream mediators TNF-␣ and MMP-9. Moreover, attenuation of the foreign body response in intraperitoneal implants in MCP-1-null mice demonstrates that the process depends on tissue-specific factors.

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“…inflammatory picture is also known in histopathology as the 'foreign body reaction' (2) . The non-parenchymal cells form organized structures or isolated cells supporting the function of the organ.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Reversible physiological transdifferentiation in the adipose organ

Cinti

2009

Proc. Nutr. Soc.

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All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.

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Cellular and Molecular Dynamics in the Foreign Body Reaction

Cited by 53 publications

References 161 publications

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants

Lack of TNF-α–Induced MMP-9 Production and Abnormal E-Cadherin Redistribution Associated with Compromised Fusion in MCP-1–Null Macrophages

Reversible physiological transdifferentiation in the adipose organ

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