title: Enhanced mesenchymal stromal cell recruitment via natural killer cells by incorporation of inflammatory signals in biomaterials.
abstract: An exacerbated inflammatory response questions biomaterial biocompatibility, but on the other hand, inflammation has a central role in the regulation of tissue regeneration. Therefore, it may be argued that an 'ideal' inflammatory response is crucial to achieve efficient tissue repair/regeneration. Natural killer (NK) cells, being one of the first populations arriving at an injury site, can have an important role in regulating bone repair/regeneration, particularly through interactions with mesenchymal stem/stromal cells (MSCs). Here, we studied how biomaterials designed to incorporate inflammatory signals affected NK cell behaviour and NK cell-MSC interactions. Adsorption of the pro-inflammatory molecule fibrinogen (Fg) to chitosan films led to a 1.5-fold increase in adhesion of peripheral blood human NK cells, without an increase in cytokine secretion. Most importantly, it was found that NK cells are capable of stimulating a threefold increase in human bone marrow MSC invasion, a key event taking place in tissue repair, but did not affect the expression of the differentiation marker alkaline phosphatase (ALP). Of significant importance, this NK cell-mediated MSC recruitment was modulated by Fg adsorption. Designing novel biomaterials leading to rational modulation of the inflammatory response is proposed as an alternative to current bone regeneration strategies.
authors.affiliation: INEB-Instituto de Engenharia Biomédica, Biomaterials Division, NEWTherapies Group, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. cralmeid@ineb.up.pt
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Almeida
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Vasconcelos
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Gonçalves
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
mesh_terms: D000327:Adsorption; D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002465:Cell Movement; D048271:Chitosan / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D012038:Regeneration
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D005340:Fibrinogen; D048271:Chitosan; D000469:Alkaline Phosphatase