title: Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro.
abstract: BACKGROUND
  The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailable. The present study was designed to provide answers to these questions by using the horse as a translational model. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC-derived conditioned medium (CM), containing all factors secreted by MSCs, on equine dermal fibroblasts, a cell type critical for successful wound healing, and (ii) explore the potential of microencapsulated equine MSCs to deliver CM to wounded cells in vitro.
  
  
  METHODS
  MSCs were isolated from the peripheral blood of healthy horses. Equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line were wounded in vitro, and cell migration and expression levels of genes involved in wound healing were evaluated after treatment with MSC-CM or NBL-6-CM. These assays were repeated by using the CM collected from MSCs encapsulated in core-shell hydrogel microcapsules.
  
  
  RESULTS
  Our salient findings were that equine MSC-derived CM stimulated the migration of equine dermal fibroblasts and increased their expression level of genes that positively contribute to wound healing. In addition, we found that equine MSCs packaged in core-shell hydrogel microcapsules had similar effects on equine dermal fibroblast migration and gene expression, indicating that microencapsulation of MSCs does not interfere with the release of bioactive factors.
  
  
  CONCLUSIONS
  Our results demonstrate that the use of CM from MSCs might be a promising new therapy for impaired cutaneous wounds and that encapsulation may be a suitable way to effectively deliver CM to wounded cells in vivo.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. lb548@cornell.edu.
authors.forename: Leen
authors.initials: L
authors.lastname: Bussche
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. rmh12@cornell.edu.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Harman
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. bas346@cornell.edu.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Syracuse
authors.affiliation: Department of Biological Sciences, State University of New York at Cortland, 21 Graham Avenue, Cortland, NY, 13045, USA. eric.plante@cortland.edu.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Plante
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Wing Road, Ithaca, NY, 14850, USA. yl2347@cornell.edu.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Biological Sciences, State University of New York at Cortland, 21 Graham Avenue, Cortland, NY, 13045, USA. theresa.curtis@cortland.edu.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Curtis
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Wing Road, Ithaca, NY, 14850, USA. mm826@cornell.edu.
authors.forename: Minglin
authors.initials: M
authors.lastname: Ma
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. grv23@cornell.edu.
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D003035:Cobalt / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D048091:Guided Tissue Regeneration / Q000379:methods; D006736:Horses; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D016685:Mitomycin / Q000494:pharmacology; D023421:Models, Animal; D012867:Skin / Q000293:injuries*; D012871:Skin Diseases / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D054357:Chemokine CXCL10; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D003035:Cobalt; D016685:Mitomycin; D007371:Interferon-gamma; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; C018021:cobaltous chloride