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Role of ECM/peptide coatings on SDF-1a triggered mesenchymal stromal cell migration from microcarriers for cell therapy
Levato, Riccardo; Planell Estany, Josep Anton; Mateos Timoneda, Miguel Ángel; Engel López, Elisabeth
Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica; Institut de Bioenginyeria de Catalunya; Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits
Many cell therapies rely on the ability of mesenchymal stromal cells (MSCs) to diffuse and localize throughout the target tissue-such as tumoral and ischemic tissues-, in response to specific cytokine signals, rather than being concentrated at the site of implantation. Therefore, it is fundamental to engineer biomaterial carriers as reservoirs, from which cells can migrate, possibly in a controlled manner. In this work, microcarriers (µCs) made of polylactic acid are characterized as MSC delivery vehicles capable of modulating key chemotactic pathways. The effect of different functionalization strategies on MSC migratory behavior from the µCs is studied in vitro in relation to SDF-1a/CXCR4 axis,-a major actor in MSC recruitment, chemotaxis and homing. Collagen and arginine-glycine-aspartic acid (RGD) peptides were either covalently grafted or physisorbed on µC surface. While stable covalent modifications promoted better cell adhesion and higher proliferation compared to physisorption, the functionalization method of the µCs also affected the cells migratory behavior in response to SDF-1a (CXCL12) stimulation. Less stable coatings (physisorbed) showed sensibly higher number of migrating cells than covalent collagen/RGD coatings. The combination of physic-chemical cues provided by protein/peptide functionalization and stimuli induced by 3D culture on µCs improved MSC expression of CXCR4, and exerted a control over cell migration, a condition suitable to promote cell homing after transplantation in vivo. These are key findings to highlight the impact of surface modification approaches on chemokine-triggered cell release, and allow designing biomaterials for efficient and controlled cell delivery to damaged tissues.
Peer Reviewed
-Àrees temàtiques de la UPC::Enginyeria dels materials
-Chemotaxis
-Biomedical engineering
-Cell therapy
-Chemotaxis
-ECM (extracellular matrix)
-Mesenchymal stromal cells
-Surface modification
-Cèl·lules canceroses
-Enginyeria biomèdica
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Article - Submitted version
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