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Semin Immunol. 2017 Feb;29:2-13. doi: 10.1016/j.smim.2017.04.004. Epub 2017 Jul 21.

Macrophage phenotype in response to ECM bioscaffolds.

Author information

1
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, PA, USA.
2
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
3
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
4
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biotechnology Engineering, Ort Braude College of Engineering, Karmiel, Israel.
5
School of Pharmacy, University of Nottingham, Nottingham, UK.
6
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, PA, USA.
7
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: badysx@upmc.edu.

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 (MECM) 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 MECM 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.

KEYWORDS:

Activation; BMDM; ECM (extracellular matrix); Macrophages; Phenotype; THP-1

PMID:
28736160
PMCID:
PMC5612880
DOI:
10.1016/j.smim.2017.04.004
[Indexed for MEDLINE]
Free PMC Article

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