title: Monitoring mesenchymal stromal cell developmental stage to apply on-time mechanical stimulation for ligament tissue engineering.
abstract: To evaluate the appropriate time frame for applying mechanical stimuli to induce mesenchymal stromal cell (MSC) differentiation for ligament tissue engineering, developmental cell phenotypes were monitored during a period of in vitro culture. MSCs were seeded onto surface-modified silk fibroin fiber matrices and cultured in Petri dishes for 15 days. Cell metabolic activity, morphology, and gene expression of extracellular matrix (ECM) proteins (collagen type I and III and fibronectin), ECM receptors (integrins alpha-2, alpha-5, and beta-1), and heat-shock protein 70 (HSP-70) were monitored during the culture of MSC. MSCs showed fluctuations in cell metabolic activity, ECM, integrin, and HSP-70 transcription potentially correlating to innate developmental processes. Cellular response to mechanical stimulation was dependent on the stage of cell development. At day 9, when levels of cell metabolic activity, ECM, integrin, and HSP-70 transcription peaked, mechanical stimulation increased MSC metabolic activity, alignment, and collagen production. Mechanical stimulation applied at day 1 and 3 showed detrimental effects on MSCs seeded on silk matrices. The results presented in this study identify a unique correlation between innate MSC development processes on a surface-modified silk matrix and dynamic environmental signaling.
authors.affiliation: Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Chen
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Horan
authors.forename: Diah
authors.initials: D
authors.lastname: Bramono
authors.forename: Jodie E
authors.initials: JE
authors.lastname: Moreau
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Laura R
authors.initials: LR
authors.lastname: Geuss
authors.forename: Adam L
authors.initials: AL
authors.lastname: Collette
authors.forename: Vladimir
authors.initials: V
authors.lastname: Volloch
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Altman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D012831:Bombyx / Q000737:chemistry; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000648:ultrastructure; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005349:Fibroins / Q000737:chemistry; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D016023:Integrins / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008022:Ligaments / Q000166:cytology* / Q000648:ultrastructure; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D013499:Surface Properties; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014158:Transcription, Genetic
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D018840:HSP70 Heat-Shock Proteins; D016023:Integrins; D005349:Fibroins