Modulating the inflammatory response - The role of Monocyte Chemotactant Protein-1
Citation for published version (APA):
Smits, A. I. P. M., Driessen - Mol, A., Bouten, C. V. C., & Baaijens, F. P. T. (2011). Modulating the inflammatory response - The role of Monocyte Chemotactant Protein-1. Poster session presented at Mate Poster Award 2011 : 16th Annual Poster Contest.
Document status and date: Published: 01/01/2011 Document Version:
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Photograph: Bart van Overbeeke
The research program of the BioMedical Materials institute is co-funded by the Dutch
Ministry of Economic Affairs, Agriculture and Innovation. The financial contribution
of the Nederlandse Hartstichting is gratefully acknowledged.
Results
MCP-1 release from the PCL/fibrin scaffolds was measured by ELISA (fig. 3). Cells were characterized by flow cytometry, revealing that the initial hPBMC suspension consisted of lymphocytes and monocytes (fig. 4A). After 16 hours in flow, the distinct CD45+ monocyte subpopulation (~8-20% of hPBMC) was no longer present in the medium, regardless of MCP-1 presence. This suggests monocyte activation by the scaffold, leading to cell adhesion and monocyte-to-macrophage differentiation (fig. 4). Moreover, addition of MCP-1 resulted in a significant increase in the M2 type macrophages inside the scaffold (fig. 4B).
Conclusion
Our results show that the PCL/fibrin scaffold evokes a response from circulating monocytes. This initial response can be modulated using MCP-1 to promote favorable M2 macrophage polarization.
hPBMC
Modulating the inflammatory response
The role of Monocyte Chemotactant Protein-1
Anthal Smits, Anita Driessen-Mol, Carlijn Bouten, Frank Baaijens
Soft Tissue Biomechanics & Engineering, Eindhoven University of Technology, The Netherlands
Introduction
Inflammation is not merely a detrimental response to biomaterial scaffolds. Rather, it can be considered as a natural agent of tissue remodeling, orchestrated by potent signaling molecules, such as monocyte chemotactant protein-1 (MCP-1)1. A biodegradable synthetic scaffold eluting a short burst of MCP-1 was shown to remodel into a fully functional healthy blood vessel via an inflammation-mediated response2. However, the exact mechanism
behind this remains unclear. We hypothesize that MCP-1 stimulates macrophage polarization towards a favorable pro-wound healing state (M2 type)3 (fig. 1).
Materials & methods
Electrospun PCL scaffolds were loaded with fibrin gel +/- MCP-1. To elucidate the response of circulating cells to the scaffolds, they were exposed to a suspension of human peripheral blood mononuclear cells (hPBMC) in pulsatile flow, using a previously validated fluidics setup4 (fig. 2).
Figure 1. Macrophages can attain various polarization states. M1 type macrophages secrete pro-inflammatory factors, while M2 macrophages promote wound healing by secreting anti-inflammatory cytokines. M2 macrophages are characterized by expression of the CD163 receptor.
Figure 2. Scaffolds were placed in a custom cross-flow chamber. hPBMC in suspension were circulated along the scaffold in a pulsatile flow with physiological pressure and shear stress.
Figure 3.
The loaded PCL/fibrin scaffolds demonstrate a burst release of MCP-1 during the first 2 hours. * Lymphocytes Monocytes Lymphocytes M2 macrophages – MCP-1 + MCP-1 t = 0 hr t = 16 hrs A. B. – MCP-1 + MCP-1
Figure 4. (A) Flow cytometry plots (left) and schematic illustration of cell-scaffold interactions (right), demonstrating the capture of CD45+
monocytes in flow into the PCL/fibrin scaffolds. (B) The amount of M2 macrophages was determined by quantifying the ratio of green CD163+
cells ( ) and the total cell count in blue DAPI staining ( ). Scale = 100µm.
[1] Mahler GJ & Butcher JT Int. J. Inflam. 2011; [2] Roh JD et al. PNAS 2010; [3] Badylak SF et al. Tissue Eng. Part A 2008; [4] Smits AIPM et al. Tissue Eng. Part C. submitted.
