PMID- 24456068 OWN - NLM STAT- MEDLINE DCOM- 20150304 LR - 20211021 IS - 1937-335X (Electronic) IS - 1937-3341 (Print) IS - 1937-3341 (Linking) VI - 20 IP - 13-14 DP - 2014 Jul TI - Dynamic vibration cooperates with connective tissue growth factor to modulate stem cell behaviors. PG - 1922-34 LID - 10.1089/ten.TEA.2013.0496 [doi] AB - Vocal fold disorders affect 3-9% of the U.S. population. Tissue engineering offers an alternative strategy for vocal fold repair. Successful engineering of vocal fold tissues requires a strategic combination of therapeutic cells, biomimetic scaffolds, and physiologically relevant mechanical and biochemical factors. Specifically, we aim to create a vocal fold-like microenvironment to coax stem cells to adopt the phenotype of vocal fold fibroblasts (VFFs). Herein, high frequency vibratory stimulations and soluble connective tissue growth factor (CTGF) were sequentially introduced to mesenchymal stem cells (MSCs) cultured on a poly(varepsilon-caprolactone) (PCL)-derived microfibrous scaffold for a total of 6 days. The initial 3-day vibratory culture resulted in an increased production of hyaluronic acids (HA), tenascin-C (TNC), decorin (DCN), and matrix metalloproteinase-1 (MMP1). The subsequent 3-day CTGF treatment further enhanced the cellular production of TNC and DCN, whereas CTGF treatment alone without the vibratory preconditioning significantly promoted the synthesis of collagen I (Col 1) and sulfated glycosaminoglycans (sGAGs). The highest level of MMP1, TNC, Col III, and DCN production was found for cells being exposed to the combined vibration and CTGF treatment. Noteworthy, the vibration and CTGF elicited a differential stimulatory effect on elastin (ELN), HA synthase 1 (HAS1), and fibroblast-specific protein-1 (FSP-1). The mitogenic activity of CTGF was only elicited in naive cells without the vibratory preconditioning. The combined treatment had profound, but opposite effects on mitogen-activated protein kinase (MAPK) pathways, Erk1/2 and p38, and the Erk1/2 pathway was critical for the observed mechano-biochemical responses. Collectively, vibratory stresses and CTGF signals cooperatively coaxed MSCs toward a VFF-like phenotype and accelerated the synthesis and remodeling of vocal fold matrices. FAU - Tong, Zhixiang AU - Tong Z AD - 1 Department of Materials Science and Engineering, Delaware Biotechnology Institute, University of Delaware , Newark, Delaware. FAU - Zerdoum, Aidan B AU - Zerdoum AB FAU - Duncan, Randall L AU - Duncan RL FAU - Jia, Xinqiao AU - Jia X LA - eng GR - P20 GM103446/GM/NIGMS NIH HHS/United States GR - R01 DC011377/DC/NIDCD NIH HHS/United States GR - R01008965/PHS HHS/United States GR - R01DC011377/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140227 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Butadienes) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Nitriles) RN - 0 (U 0126) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Biomechanical Phenomena/drug effects MH - Bioreactors MH - Blotting, Western MH - Butadienes/pharmacology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Connective Tissue Growth Factor/*pharmacology MH - Extracellular Matrix Proteins/drug effects/metabolism MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Mesenchymal Stem Cells/*cytology/drug effects/enzymology MH - Nitriles/pharmacology MH - Time Factors MH - *Vibration PMC - PMC4086222 EDAT- 2014/01/25 06:00 MHDA- 2015/03/05 06:00 PMCR- 2015/07/01 CRDT- 2014/01/25 06:00 PHST- 2014/01/25 06:00 [entrez] PHST- 2014/01/25 06:00 [pubmed] PHST- 2015/03/05 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] AID - 10.1089/ten.tea.2013.0496 [pii] AID - 10.1089/ten.TEA.2013.0496 [doi] PST - ppublish SO - Tissue Eng Part A. 2014 Jul;20(13-14):1922-34. doi: 10.1089/ten.TEA.2013.0496. Epub 2014 Feb 27.