title: Shear stress and circumferential stretch by pulsatile flow direct vascular endothelial lineage commitment of mesenchymal stem cells in engineered blood vessels.
abstract: Understanding the response of mesenchymal stem cells (MSCs) in the dynamic biomechanical vascular environment is important for vascular regeneration. Native vessel biomechanical stimulation in vitro is thought to be the most important contributor to successful endothelial differentiation of MSCs. However, the appropriate biomechanical stimulation conditions for differentiating MSCs into ECs have not been fully investigated. To accomplish an in vivo-like loading environment, a loading system was designed to apply flow induced stress and induce hMSC differentiation in vascular cells. Culturing MSCs on tubular scaffolds under flow-induced shear stress (2.5 dyne/cm(2)) for 4 days results in increased mRNA levels of EC markers (vWF, CD31, VE-cadherin and E-selectin) after one day. Furthermore, we investigated the effects of 2.5 dyne/cm(2) shear stress followed by 3% circumferential stretch for 3 days, and an additional 5% circumferential stretch for 4 days on hMSC differentiation into ECs. EC marker protein levels showed a significant increase after applying 5% stretch, while SMC markers were not present at levels sufficient for detection. Our results demonstrate that the expression of several hMSC EC markers cultured on double-layered tubular scaffolds were upregulated at the mRNA and protein levels with the application of fluid shear stress and cyclic circumferential stretch.
authors.affiliation: Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea.|Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA, 19104-6081, USA.
authors.forename: Dong Hwa
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA, 19104-6081, USA.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea.
authors.forename: Yun Gyeong
authors.initials: YG
authors.lastname: Kang
authors.affiliation: Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea. sjw@bme.inje.ac.kr.|Department of Health Science and Technology, Institute of Aged Life Redesign, Cardiovascular and Metabolic Disease Center, UHRC, Inje University, Gimhae, Gyeongnam, 621-749, Republic of Korea. sjw@bme.inje.ac.kr.
authors.forename: Jung-Woog
authors.initials: JW
authors.lastname: Shin
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D033081:Shear Strength; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods
chemical_list: D005456:Fluorescent Dyes