title: Effect of human Wharton's jelly mesenchymal stem cell paracrine signaling on keloid fibroblasts.
abstract: Keloid scars are abnormal benign fibroproliferative tumors with high recurrence rates and no current efficacious treatment. Accumulating evidence suggests that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have antifibrotic properties. Paracrine signaling is considered one of the main underlying mechanisms behind the therapeutic effects of mesenchymal stem cells. However, the paracrine signaling effects of WJ-MSCs on keloids have not yet been reported. The aim of this study is to investigate paracrine signaling effects of human WJ-MSCs on keloid fibroblasts in vitro. Human umbilical cords and keloid skin samples were obtained, and WJ-MSCs and keloid fibroblasts were isolated and cultured. One-way and two-way paracrine culture systems between both cell types were investigated. Plasminogen activator inhibitor-I and transforming growth factor-β2 (TGF-β2) transcripts were upregulated in keloid fibroblasts cultured with WJ-MSC-conditioned medium (WJ-MSC-CM) and cocultured with inserts, while showing lower TGF-β3 gene expression. Interleukin (IL)-6, IL-8, TGF-β1, and TGF-β2 protein expression was also enhanced. The WJ-MSC-CM-treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability. In our culture conditions, the indirect application of WJ-MSCs on keloid fibroblasts may enhance their profibrotic phenotype.
authors.affiliation: Plastic Surgery Department and Burn Unit, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain; Ross Tilley Burn Centre and Sunnybrook Research Institute and Gynecology and Obstetrics Department, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anna I
authors.initials: AI
authors.lastname: Arno
authors.forename: Saeid
authors.initials: S
authors.lastname: Amini-Nik
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Blit
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Shehab
authors.forename: Cassandra
authors.initials: C
authors.lastname: Belo
authors.forename: Elaine
authors.initials: E
authors.lastname: Herer
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D015194:Diffusion Chambers, Culture; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007627:Keloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism; D059631:Wharton Jelly / Q000166:cytology / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
keywords: Fibrosis; Keloid; Scar; Skin; Stem cells; Wharton’s jelly