title: Role of ECM/peptide coatings on SDF-1α triggered mesenchymal stromal cell migration from microcarriers for cell therapy.
abstract: 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-1α/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-1α (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.
authors.affiliation: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER en Biomateriales, Bioingeniería y Nanomedicina (CIBER-BBN), Spain.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Levato
authors.affiliation: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Planell
authors.affiliation: CIBER en Biomateriales, Bioingeniería y Nanomedicina (CIBER-BBN), Spain; Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. Electronic address: mamateos@ibecbarcelona.eu.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Mateos-Timoneda
authors.affiliation: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; CIBER en Biomateriales, Bioingeniería y Nanomedicina (CIBER-BBN), Spain; Department of Materials Science and Metallurgy, Technical University of Catalonia, Barcelona, Spain.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Engel
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008863:Microspheres; D010455:Peptides / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D020099:Coated Materials, Biocompatible; D010455:Peptides; D019718:Receptors, CXCR4
keywords: Cell therapy; Chemotaxis; ECM (extracellular matrix); Mesenchymal stromal cells; Surface modification