PMID- 27345475 OWN - NLM STAT- MEDLINE DCOM- 20170804 LR - 20181202 IS - 1531-4995 (Electronic) IS - 0023-852X (Print) IS - 0023-852X (Linking) VI - 127 IP - 1 DP - 2017 Jan TI - Mesenchymal stem cells have antifibrotic effects on transforming growth factor-beta1-stimulated vocal fold fibroblasts. PG - E35-E41 LID - 10.1002/lary.26121 [doi] AB - OBJECTIVES/HYPOTHESIS: Mesenchymal stem cells (MSCs) hold therapeutic promise for vocal fold scar, yet the precise mechanism(s) underlying tissue level changes remain unclear. We hypothesize that MSCs interact with native fibroblasts to favorably affect healing. Furthermore, we hypothesize that these interactions vary based on MSC source. METHODS: Vocal fold fibroblasts (VFFs), adipose-derived stem cells, and bone marrow-derived stem cells (BMSCs) were extracted from Sprague-Dawley rats; and a coculture model was employed culturing VFFs +/- transforming growth factor (TGF-beta1) (10 ng/mL) +/- MSCs. Monoculture MSCs were also prepared as a control. Both extracellular matrix (ECM) and components of the TGF-beta signaling pathway were analyzed via polymerase chain reaction and western blotting. RESULTS: Significantly decreased TGF-beta1 mRNA and alpha-smooth muscle actin protein was observed in VFFs in response to TGF-beta1 in the coculture with both MSCs (P < 0.05, P < 0.01). BMSCs significantly downregulated collagen I (P < 0.05), collagen III (P < 0.05), Smad3 (P < 0.01), and TGF-beta1 receptor I (P < 0.01) mRNA in VFFs. Hyaluronic synthase-1 and 2 increased in cocultured BMSCs when compared with monocultured BMSCs at baseline and in response to TGF-beta1 (P < 0.01). CONCLUSION: MSCs had a favorable effect on ECM regulation as well as suppression of TGF-beta1 signaling in VFF. Bidirectional paracrine signaling was also observed as VFFs altered ECM regulation in MSCs. These data provide insight into the regenerative effects of MSCs and provide a foundation for clinical application. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E35-E41, 2017. CI - (c) 2016 The American Laryngological, Rhinological and Otological Society, Inc. FAU - Hiwatashi, Nao AU - Hiwatashi N AD - NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York, U.S.A. FAU - Bing, Renjie AU - Bing R AD - NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York, U.S.A. FAU - Kraja, Iv AU - Kraja I AD - NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York, U.S.A. FAU - Branski, Ryan C AU - Branski RC AD - NYU Voice Center, Department of Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, New York, U.S.A. LA - eng GR - R01 DC013277/DC/NIDCD NIH HHS/United States PT - Journal Article DEP - 20160627 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Adipose Tissue/cytology MH - Animals MH - Blotting, Western MH - Bone Marrow Cells/metabolism MH - Cell Differentiation/drug effects MH - Coculture Techniques MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - Fibroblasts/*metabolism MH - Mesenchymal Stem Cells/*cytology MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Transforming Growth Factor beta1/*metabolism MH - Vocal Cords/*cytology/*metabolism PMC - PMC5177483 MID - NIHMS786473 OTO - NOTNLM OT - TGF-beta OT - Vocal fold OT - extracellular matrix OT - fibrosis OT - mesenchymal stem cells OT - voice EDAT- 2016/06/28 06:00 MHDA- 2017/08/05 06:00 PMCR- 2018/01/01 CRDT- 2016/06/28 06:00 PHST- 2016/03/24 00:00 [received] PHST- 2016/04/25 00:00 [revised] PHST- 2016/05/09 00:00 [accepted] PHST- 2016/06/28 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] PHST- 2016/06/28 06:00 [entrez] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.1002/lary.26121 [doi] PST - ppublish SO - Laryngoscope. 2017 Jan;127(1):E35-E41. doi: 10.1002/lary.26121. Epub 2016 Jun 27.