Macrophage phenotypes correspond with remodeling outcomes of various acellular dermal matrices

Agrawal, Hitesh; Tholpady, Sunil S.; Capito, Anthony E.; Drake, David B.; Katz, Adam J.

doi:10.4236/ojrm.2012.13008

Cited by 23 publications

(33 citation statements)

References 25 publications

(32 reference statements)

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“…The ratio of MR+ (M2-marker (Agrawal, 2012;Mantovani, 2006;Choi et al, 2010)) cells to Calprotectin+ (M1-marker (Bartneck et al, 2010)) cells was ∼3 on PS and decreased to ∼1 on O 2 -PS40 (Fig. 2).…”

Section: Discussionmentioning

confidence: 90%

“…In contrast, M2 macrophages secrete large amounts of anti-inflammatory and pro-fibrotic cytokines such as IL-10 (Mantovani, 2006), transforming growth factor (TGF-␤) (Hao et al, 2012), and IL-1 receptor antagonist (IL-1RA) (Baitsch et al, 2011). In addition, these cells express high levels of mannose receptor (MR) (Agrawal, 2012;Mantovani, 2006;Choi et al, 2010) and the scavenger receptor CD163 (Edin et al, 2012;Mantovani, 2006).…”

Section: Introductionmentioning

confidence: 92%

“…They are also characterised by elevated expression of the chemokine (C-C motif) receptor 7 (CCR7) (Agrawal, 2012), CCR2 (Willenborg et al, 2012), calprotectin (Bartneck et al, 2010), and nitric oxide synthase 2, inducible (NOS2) (Edin et al, 2012). In contrast, M2 macrophages secrete large amounts of anti-inflammatory and pro-fibrotic cytokines such as IL-10 (Mantovani, 2006), transforming growth factor (TGF-␤) (Hao et al, 2012), and IL-1 receptor antagonist (IL-1RA) (Baitsch et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

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The impact of surface chemistry modification on macrophage polarisation

et al. 2016

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Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 96%

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The impact of surface chemistry modification on macrophage polarisation

et al. 2016

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“…In this study, macrophages predictably increased or decreased gene expression of known markers of macrophage phenotype when the environmental stimuli were switched, but expression and secretion of the angiogenic proteins VEGF and PDGF were less predictable. Further research is required to investigate the role of these hybrid phenotypes in regulating angiogenesis, especially considering that “mixed” phenotypes have been associated with blood vessel development and scaffold vascularization [20, 21, 52]. Another interesting result was that M2 macrophages proliferated in vitro , which was recently described in vivo as a normal response to IL4 [53].…”

Section: Discussionmentioning

confidence: 99%

Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds

et al. 2015

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In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing. To this end, we first analyzed the in vitro kinetics of macrophage phenotype switch using flow cytometry, gene expression, and cytokine secretion analysis. Then, we designed scaffolds for bone regeneration based on modifications of decellularized bone for a short release of interferon-gamma (IFNg) to promote the M1 phenotype, followed by a more sustained release of interleukin-4 (IL4) to promote the M2 phenotype. To achieve this sequential release profile, IFNg was physically adsorbed onto the scaffolds, while IL4 was attached via biotin-streptavidin binding. Interestingly, despite the strong interactions between biotin and streptavidin, release studies showed that biotinylated IL4 was released over 6 days. These scaffolds promoted sequential M1 and M2 polarization of primary human macrophages as measured by gene expression of ten M1 and M2 markers and secretion of four cytokines, although the overlapping phases of IFNg and IL4 release tempered polarization to some extent. Murine subcutaneous implantation model showed increased vascularization in scaffolds releasing IFNg compared to controls. This study demonstrates that scaffolds for tissue engineering can be designed to harness the angiogenic behavior of host macrophages towards scaffold vascularization.

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“…Therefore, we speculate that both functionally active populations of pro- and anti-inflammatory cells (e.g., M1 and M2 macrophage phenotypes) are important for de novo regeneration of VML injured skeletal muscle. In support of this speculation, other studies have also demonstrated that coordinated efforts by both M1 and M2 macrophage phenotypes are necessary for scaffold vascularization [42] and remodeling [43] . A recent study by Novak et al ., reported that macrophage populations present after muscle laceration injury, did not conform to the canonical M1/M2 classification.…”

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confidence: 83%

Asynchronous inflammation and myogenic cell migration limit muscle tissue regeneration mediated by acellular scaffolds

Garg

Ward

Corona

2014

Inflamm Cell Signal

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Volumetric muscle loss (VML) following orthopaedic trauma results in chronic loss of strength and can contribute to disability. Tissue engineering and regenerative medicine approaches to regenerate the lost skeletal muscle and improve functional outcomes are currently under development. At the forefront of these efforts, decellularized extracellular matrices (ECMs) have reached clinical testing and provide the foundation for other approaches that include stem/progenitor cell delivery. ECMs have been demonstrated to possess many qualities to initiate regeneration, to include stem cell chemotaxis and pro-regenerative macrophage polarization. However, the majority of observations indicate that ECM-repair of VML does not promote appreciable muscle fiber regeneration. In a recent study, ECM-repair of VML was compared to classical muscle fiber regeneration (Garg et al., 2014, Cell & Tissue Research) mediated by autologous minced grafts. The most salient findings of this study were: 1) Satellite cells did not migrate into the scaffold beyond ~0.5 mm from the remaining host tissue, although other migratory stem cells (Sca-1+) were observed throughout the scaffold;2) Macrophage migration to the scaffold was over two-times that observed with muscle grafts, but they appeared to be less active, as gene expression of pro- and anti-inflammatory cytokines (TNF-α, IL-12, IL-4, IL-10, VEGF, and TGF-β1) was significantly reduced in scaffold-repaired muscles; And, 3) scaffolds did not promote appreciable muscle fiber regeneration. Collectively, these data suggest that the events following ECM transplantation in VML are either incongruous or asynchronous with classical muscle fiber regeneration.

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Macrophage phenotypes correspond with remodeling outcomes of various acellular dermal matrices

Abstract: ABSTRACT

Cited by 23 publications

References 25 publications

The impact of surface chemistry modification on macrophage polarisation

The impact of surface chemistry modification on macrophage polarisation

Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds

Asynchronous inflammation and myogenic cell migration limit muscle tissue regeneration mediated by acellular scaffolds

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