Cited by 169Wound Healing and TreatmentsImmune cells in cancerTissue Engineering and Regenerative Medicine

Macrophage phenotype in response to ECM bioscaffolds

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Huleihel, Luai, Dziki, Jenna L., Bartolacci, Joseph G., Rausch, Theresa, Scarritt, Michelle E., Cramer, Madeline C., Vorobyov, Tatiana, LoPresti, Samuel T. +4 more·2017·Seminars in Immunology

Abstract

Macrophage presence and phenotype are critical determinants of the healing response following injury. Downregulation of the pro-inflammatory macrophage phenotype has been associated with the therapeutic use of bioscaffolds composed of extracellular matrix (ECM), but phenotypic characterization of macrophages has typically been limited to small number of non-specific cell surface markers or expressed proteins. The present study determined the response of both primary murine bone marrow derived macrophages (BMDM) and a transformed human mononuclear cell line (THP-1 cells) to degradation products of two different, commonly used ECM bioscaffolds; urinary bladder matrix (UBM-ECM) and small intestinal submucosa (SIS-ECM). Quantified cell responses included gene expression, protein expression, commonly used cell surface markers, and functional assays. Results showed that the phenotype elicited by ECM exposure (M ECM) is distinct from both the classically activated IFNγ+LPS phenotype and the alternatively activated IL-4 phenotype. Furthermore, the BMDM and THP-1 macrophages responded differently to identical stimuli, and UBM-ECM and SIS-ECM bioscaffolds induced similar, yet distinct phenotypic profiles. The results of this study not only characterized an M ECM phenotype that has anti-inflammatory traits but also showed the risks and challenges of making conclusions about the role of macrophage mediated events without consideration of the source of macrophages and the limitations of individual cell markers.

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Crossref · 10.1016/j.smim.2017.04.004

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  • During degradation of implanted ECM bioscaffolds, ECM components are released and promote the transition to a remodeling phase.

    “What is more, it is widely accepted that during the degradation of implanted ECM bioscaffolds, ECM components are released into the environment and promote the transition to a remodeling phase [18,44,74,78].”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [44]

    The Methods (§3.2) describe producing ECM degradation products, and the Discussion (§4.3) reports that those products down-regulated inflammatory markers in pre-activated macrophages, consistent with constructive remodeling. The paper does not establish that implanted scaffolds release components into their surroundings or that this release causes a transition to a distinct remodeling phase. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • ECM degradation peptides promote M2-like phenotypes in vitro and in vivo.

    “promotion of M2-like phenotypes in vitro [40,44,153] and in vivo [152,154,155].”

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Research works printed but not linked: 1

  1. [31]https://www.ncbi.nlm.nih.gov/gene/.

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Authors
Huleihel, L., Dziki, J. L., Bartolacci, J. G., Rausch, T., Scarritt, M. E., Cramer, M. C., Vorobyov, T., LoPresti, S. T., Swineheart, I. T., White, L. J., Brown, B. N., & Badylak, S. F.
Affiliations
  • University of Pittsburgh (US)
  • University of Nottingham (GB)
Corresponding author
Badylak, Stephen F.
Venue
Seminars in Immunology
Publisher
Elsevier BV
Published
2017-02
Volume
29
Pages
2-13
ISSN
1044-5323 (ISSN-L)
OpenAlex
W2737628422
Cited by
169
References
81
Citations by year
2026: 8 · 2025: 21 · 2024: 19 · 2023: 19 · 2022: 19 · 2021: 28 · 2020: 23 · 2019: 13 · 2018: 16 · 2017: 3
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Seminars in Immunology (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Nottingham ePrints (University of Nottingham) (submittedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (RO1DE022055)
  • Department of defense (W81XWH-15-1-0026)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
macrophage phenotype, urinary bladder matrix, small intestinal submucosa, bone marrow-derived macrophages, THP-1 cells, macrophage polarization, anti-inflammatory macrophages, inflammatory macrophages, cell surface markers, tissue repair
MeSH terms
Animals, Biocompatible Materials, Bone Marrow Cells, Cell Differentiation, Extracellular Matrix, Humans, Macrophages, Mammals, Phenotype, Wound Healing, Biomimetics, Tissue Scaffolds

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