Effect of Human Wharton's Jelly Mesenchymal Stem Cell Paracrine Signaling on Keloid Fibroblasts

• Published in: Stem cells translational medicine Vol. 3; no. 3; pp. 299 - 307
• Main Authors: Arno, Anna I., Amini-Nik, Saeid, Blit, Patrick H., Al-Shehab, Mohammed, Belo, Cassandra, Herer, Elaine, Jeschke, Marc G.
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01-03-2014; Oxford University Press
• Subjects: Administrative support; Apoptosis; Bone marrow; Cancer; Cell culture; Cell Proliferation - drug effects; Coculture Techniques; Culture Media, Conditioned - pharmacology; Data analysis; Diffusion Chambers, Culture; Fetal and Neonatal Stem Cells; Fetal Blood - cytology; Fetal Blood - metabolism; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gene expression; Gene Expression Regulation; Genotype & phenotype; Health sciences; Humans; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Keloid; Keloid - genetics; Keloid - metabolism; Keloid - pathology; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Paracrine Communication - drug effects; Paracrine signalling; Phenotypes; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Primary Cell Culture; Scar; Scars; Skin; Stem cells; Transforming growth factor; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming Growth Factor beta2 - genetics; Transforming Growth Factor beta2 - metabolism; Transforming Growth Factor beta3 - genetics; Transforming Growth Factor beta3 - metabolism; Transforming growth factor-b1; Trauma; Tumors; Umbilical cord; Wharton Jelly - cytology; Wharton Jelly - metabolism; Wharton's jelly; Skin; Wharton’s jelly; Keloid; Scar; Fibrosis; Stem cells
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2013-0120

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.
This study investigated paracrine signaling effects of human Wharton's jelly‐derived mesenchymal stem cells (WJ‐MSCs) on keloid fibroblasts in vitro. The WJ‐MSC‐conditioned medium‐treated keloid fibroblasts showed higher proliferation rates than their control keloid fibroblasts with no significant change in apoptosis rate or migration ability.