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Macrophage phenotype in response to ECM bioscaffolds

Huleihel, Luai; Dziki, Jenna L.; Bartolacci, Joseph G.; Rausch, Theresa; Scarritt, Michelle E.; Cramer, Madeline C.; Vorobyov, Tatiana; LoPresti, Samuel T.; Swinehart, Ilea T.; White, Lisa J.; Brown, Bryan N.; Badylak, Stephen F

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Luai Huleihel

Jenna L. Dziki

Joseph G. Bartolacci

Theresa Rausch

Michelle E. Scarritt

Madeline C. Cramer

Tatiana Vorobyov

Samuel T. LoPresti

Ilea T. Swinehart

Bryan N. Brown

Stephen F Badylak


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 IFN? + 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.

Journal Article Type Article
Acceptance Date Apr 25, 2017
Online Publication Date Jul 21, 2017
Publication Date Feb 1, 2017
Deposit Date Sep 15, 2017
Publicly Available Date Sep 15, 2017
Journal Seminars in Immunology
Print ISSN 1044-5323
Electronic ISSN 1096-3618
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 29
Keywords ECM (extracellular matrix); macrophages; activation; THP-1; BMDM; phenotype
Public URL
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