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Shear stress and circumferential stretch by pulsatile flow direct vascular endothelial lineage commitment of mesenchymal stem cells in engineered blood vessels

  • Tissue Engineering Constructs and Cell Substrates
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

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/cm2) 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/cm2 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.

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Acknowledgments

This work was supported by grants from the Technology Innovation Program (10038667, Ministry of Knowledge Economy, ROK) and Priority Research Centers Program (2010-0020224, the Ministry of Education, Science and Technology).

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Authors and Affiliations

  1. Department of Biomedical Engineering, Inje University, Rm #309, BLDG-A, 607 Obang-Dong, Gimhae, Gyeongnam, 621-749, Republic of Korea

    Dong Hwa Kim, Yun Gyeong Kang, Ji Won Shin, So Hee Park & Jung-Woog Shin

  2. Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, 36th Street and Hamilton Walk, 424 Stemmler Hall, Philadelphia, PA, 19104-6081, USA

    Dong Hwa Kim & Su-Jin Heo

  3. 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

    Jung-Woog Shin

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  1. Dong Hwa Kim
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Correspondence to Jung-Woog Shin.

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Kim, D.H., Heo, SJ., Kang, Y.G. et al. Shear stress and circumferential stretch by pulsatile flow direct vascular endothelial lineage commitment of mesenchymal stem cells in engineered blood vessels. J Mater Sci: Mater Med 27, 60 (2016). https://doi.org/10.1007/s10856-016-5670-0

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  • DOI: https://doi.org/10.1007/s10856-016-5670-0

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