Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

Valentin, Jolene E.; Stewart‐Akers, Ann M.; Gilbert, Thomas W.; Badylak, Stephen F.

doi:10.1089/ten.tea.2008.0419

Cited by 310 publications

(270 citation statements)

References 55 publications

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“…The parallel increase in FoxP3 + T cells in the tissues surrounding the decellularized tissue implants suggests that these regulatory cells may have a role in the local modulation of the rejection response. The predominant phenotype of resident macrophages can provide an indication of scaffold rejection (inflammation) or acceptance following implantation as shown (32,(33)(34)(35)(36)(37)(38)(39)(40). M1-activated macrophages express IL-12 high , IL-23 high , and IL-10 low and produce inflammatory cytokines such as IL-1β, IL-6, and TNFα, which promote active inflammation, ECM destruction, and tissue injury.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Fishman

Lowdell

Urbani³

et al. 2013

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

184

137

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Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissueengineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cellmediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Fishman

Lowdell

Urbani³

et al. 2013

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

184

137

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“…S1) and systemically (50), promote a local microenvironmental niche that facilitates stem cell recruitment and/or maintenance (51-53). An independent contributing factor to the host response is the effect of ECM scaffolds on tissue macrophages (33,(54)(55)(56) and T cells (57). Macrophages are critical determinants of the overall regenerative response in vivo (56).…”

Section: Discussionmentioning

confidence: 99%

“…An independent contributing factor to the host response is the effect of ECM scaffolds on tissue macrophages (33,(54)(55)(56) and T cells (57). Macrophages are critical determinants of the overall regenerative response in vivo (56). Inhibition of ECM scaffold degradation in vivo alters macrophage polarization toward a proinflammatory phenotype (54).…”

Section: Discussionmentioning

confidence: 99%

Epimorphic regeneration approach to tissue replacement in adult mammals

Agrawal

Johnson²,

Reing³

et al. 2009

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

Self Cite

143

134

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Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor and stem cells to a site of injury. Bioactive molecules resulting from degradation of extracellular matrix (ECM) have been shown to recruit a variety of progenitor and stem cells in vitro in adult mammals. The ability to recruit multipotential cells to the site of injury by in vivo administration of chemotactic ECM degradation products in a mammalian model of digit amputation was investigated in the present study. Adult, 6- to 8-week-old C57/BL6 mice were subjected to midsecond phalanx amputation of the third digit of the right hind foot and either treated with chemotactic ECM degradation products or left untreated. At 14 days after amputation, mice treated with ECM degradation products showed an accumulation of heterogeneous cells that expressed markers of multipotency, including Sox2, Sca1, and Rex1 (Zfp42). Cells isolated from the site of amputation were capable of differentiation along neuroectodermal and mesodermal lineages, whereas cells isolated from control mice were capable of differentiation along only mesodermal lineages. The present findings demonstrate the recruitment of endogenous stem cells to a site of injury, and/or their generation/proliferation therein, in response to ECM degradation products.

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“…It has been reported earlier that the in vitro degradation of scaffold differs from in vivo degradation process as various matrix metalloproteinases [69] and macrophages [70,71] are responsible for degrading biological scaffold materials in vivo. The in vitro biodegradation of decellularized lung scaffold by 0.2% concentration of collagenase was used as an 'accelerated model' of degradation and the collagenase activities in vivo are not expected to be as harsh as in vitro [72].…”

Section: In Vitro Biodegradation Of Decellularized Goat-lung Matrixmentioning

confidence: 99%

Antibacterial activity and composition of decellularized goat lung extracellular matrix for its tissue engineering applications

Gupta¹,

Dinda²,

Mishra³

2017

Biol Eng Med

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In this study, scaffold was fabricated from goat-lung of cadaver goat by decellularization method for its potential application in tissue engineering. The cellular components of goat-lung were removed by employing trypsin-SDS based method of decellularization. DNA quantification and DAPI staining verified the effective removal of native cells from the goat-lung. Verhoeff-Van Gieson (VVG) staining, H&E staining and Periodic-Acid Schiff (PAS) staining histologically assessed the composition of native and decellularized goat-lung matrix-demonstrating the presence of collagen, elastin and glycoproteins in the decellularized goat-lung matrix. Antibacterial activity of decellularized goat-lung matrix was evaluated against gram-negative (Escherichiacoli) and gram-positive (Staphylococcusaureus) bacteria, which shows the presence of naturally occurring bioactive peptides-exhibiting the antibacterial activity against E. coli for up to 9h and against S. aureus for up to 5h. The decellularized goat-lung matrix, as demonstrated by MTT assay, was found to be biocompatibile to L929 mouse fibroblasts, HepG2, human skin derived mesenchymal stem cells (hS-MSCs), osteoblasts and BMMSCs. All the above results confer the applicability of the decellularized goat-lung matrix as a potential scaffold for tissue engineering applications.

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Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

Cited by 310 publications

References 55 publications

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Epimorphic regeneration approach to tissue replacement in adult mammals

Antibacterial activity and composition of decellularized goat lung extracellular matrix for its tissue engineering applications

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