Macrophage phenotype in response to ECM bioscaffolds

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.

Extracellular Matrix Bioscaffolds as Immunomodulatory Biomaterials

“…80,81 Sicari et al have shown that degradation products of ECM bioscaffolds can directly activate macrophages toward a iNOS -/Fizz1 + macrophage phenotype. 25 Furthermore, Huleihel et al 82 conducted an exhaustive analysis of macrophage phenotype following exposure to ECM degradation products showing that ECM is consistently associated with downregulation of pro-inflammatory genes and proteins. The ability of ECM bioscaffolds to activate macrophages is well established.…”

Enhanced Vascular Biocompatibility and Remodeling of Decellularized and Secured Xenogeneic/Allogeneic Matrices in a Porcine Model

“…In recent studies, some authors showed decellularized scaffolds polarize the macrophage response in vivo toward an M2 phenotype, an alternative pathway activation of macrophages [24, 28, 29]. Future studies with M1/M2 phenotypes will investigate this finding in DHP and DPPt.…”

Harnessing Inorganic Nanoparticles to Direct Macrophage Polarization for Skeletal Muscle Regeneration

“…In this context, a recent study comparing macrophage activation after exposure to dECM derived from different tissues, highlighted heterogeneity in macrophage response due to distinct ECM degradation products. In particular, the exposure to urinary bladder matrix or small intestinal submucosa ECM differently affected murine bone marrow-derived macrophages, generating distinct gene expression profiles of several commonly investigated macrophage surface and activation markers [ 27 ]. Scaffolds deriving from the same tissue may also behave differently; dECM from skeletal muscle, for example, has been shown to trigger macrophage polarization towards the M2 anti-inflammatory phenotype in an in vivo model of skeletal tissue injury [ 28 ], but other studies reported no impact of skeletal muscle-derived ECM on macrophage plasticity [ 10 ].…”