These authors contributed equally to this work.
In vitro characterization of macrophage interaction with mesenchymal stromal cell-hyaluronan hydrogel constructs
Version of Record online: 24 JUN 2013
Copyright © 2013 Society of Plastics Engineers
Journal of Biomedical Materials Research Part A
Volume 102, Issue 3, pages 890–902, March 2014
How to Cite
How to cite this article: 2014. In vitro characterization of macrophage interaction with mesenchymal stromal cell-hyaluronan hydrogel constructs. J Biomed Mater Res Part A 2014:102A: 890–902., , , , , .
- Issue online: 16 JAN 2014
- Version of Record online: 24 JUN 2013
- Accepted manuscript online: 8 APR 2013 03:21AM EST
- Manuscript Accepted: 28 MAR 2013
- Manuscript Revised: 22 MAR 2013
- Manuscript Received: 14 DEC 2012
- NIDCD – NIH. Grant Numbers: R01 DC4336, R01 DC4336S1, T32 DC009401
- NHLBI – NIH. Grant Number: K08 HL081076
- mesenchymal stromal/stem cells;
- tissue engineering;
- hyaluronic acid
Macrophages play a critical role in mediating not only normal tissue healing, but also the host reaction against biomaterial scaffolds. There is increasing interest in regenerative medicine to combine mesenchymal stromal/stem cells (MSCs) with biomaterial scaffolds to modulate inflammatory response while restoring tissue architecture. The objective of the current study was to investigate the interaction between MSCs (derived from bone marrow, adipose or vocal fold tissue) encapsulated in hyaluronan-based hydrogel and differentiating macrophages as measured by extracellular matrix (ECM) gene expression and cytokine, chemokine, and growth factor concentrations. Gene expression was analyzed using real-time polymerase chain reaction from MSCs embedded in Carbylan-GSX after 7 days of coculture with or without CD14+ cells. Protein concentrations were measured using a Bio-plex assay from cell culture supernatants on days 3 and 7 for all conditions. Following 7 days, we identified upregulation of collagen-I, collagen-III, procollagen, and matrix metalloproteinase-9 genes compared to control conditions. We demonstrate increased concentrations of immunoregulatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α, macrophage inflammatory protein-1α, IFN-γ, IL-12, and IL-10] and remodeling growth factors (vascular endothelial growth factor, hepatocyte growth factor) in MSC-3D constructs cocultured with macrophages compared to control conditions, with some temporal variation. Our results indicate an alteration of expression of ECM proteins important to tissue regeneration and cytokines critical to the inflammatory cascade when 3D constructs were cultured with differentiating macrophages. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 890–902, 2014.