title: Surgical meshes coated with mesenchymal stem cells provide an anti-inflammatory environment by a M2 macrophage polarization.
abstract: Surgical meshes are widely used in clinics to reinforce soft tissue's defects, and to give support to prolapsed organs. However, the implantation of surgical meshes is commonly related with an inflammatory response being difficult to eradicate without removing the mesh. Here we hypothesize that the combined use of surgical meshes and mesenchymal stem cells (MSCs) could be a useful tool to reduce the inflammatory reaction secondary to mesh implantation. In vitro determinations of viability, metabolic activity and immunomodulation assays were performed on MSCs-coated meshes. Magnetic resonance imaging, evaluation by laparoscopic optical system and histology were performed for safety assessment. Finally, flow cytometry and qRT-PCR were used to elucidate the mechanism of action of MSCs-coated meshes. Our results demonstrate the feasibility to obtain MSCs-coated surgical meshes and their cryopreservability to be used as an 'off the shelf' product. These biological meshes fulfill the safety aspects as non-adverse effects were observed when compared to controls. Moreover, both in vitro and in vivo studies demonstrated that, local immunomodulation of implanted meshes is mediated by a macrophage polarization towards an anti-inflammatory phenotype. In conclusion, the combined usage of surgical meshes with MSCs fulfills the safety requirements for a future clinical application, providing an anti-inflammatory environment that could reduce the inflammatory processes commonly observed after surgical mesh implantation.
  
  
  CONCLUSIONS
  Surgical meshes are medical devices widely used in clinics to resolve hernias and organs' prolapses, among other disorders. However, the implantation of surgical meshes is commonly related with an inflammatory response being difficult to eradicate without removing the mesh, causing pain and discomfort in the patient. Previously, the anti-inflammatory, immunomodulatory and pro-regenerative ability of mesenchymal stem cells (MSCs) have been described. To our knowledge, this is the first report where the anti-inflammatory and pro-regenerative ability of MSCs have been successfully applied in combination with surgical meshes, reducing the inflammatory processes commonly observed after mesh implantation. Moreover, our in vitro and in vivo results highlight the safety and efficacy of these bioactive meshes as a 'ready to use' medical product.
authors.affiliation: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres 10071, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Blázquez
authors.affiliation: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres 10071, Spain.
authors.forename: Francisco Miguel
authors.initials: FM
authors.lastname: Sánchez-Margallo
authors.affiliation: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres 10071, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Álvarez
authors.affiliation: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres 10071, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Usón
authors.affiliation: Stem Cell Therapy Unit, 'Jesús Usón' Minimally Invasive Surgery Centre, Cáceres 10071, Spain. Electronic address: jgarcia@ccmijesususon.com.
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002469:Cell Separation; D002470:Cell Survival; D015925:Cryopreservation; D003470:Culture Media / Q000737:chemistry; D005434:Flow Cytometry; D005549:Foreign-Body Reaction / Q000473:pathology; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010641:Phenotype; D011126:Polypropylenes / Q000378:metabolism; D019736:Prostheses and Implants; D013526:Surgical Mesh; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D003470:Culture Media; D011126:Polypropylenes; D007371:Interferon-gamma
keywords: Biocompatibility; Foreign body response; Mesenchymal stem cell; Surgical mesh