Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading

Haiying Huang, Yasuhide Nakayama, Kairong Qin, Kimiko Yamamoto, Joji Ando, Jun Yamashita, Hiroshi Itoh, Keiichi Kanda, Hitoshi Yaku, Yoshihiro Okamoto, Yasushi Nemoto

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76 Citations (Scopus)


This study evaluated the possibility of differentiation from embryonic stem (ES) cells to vascular wall cells by physical (mechanical) stress loading in vitro. A cell mixture containing Flk1-positive cells (ca. 30%) derived from murine ES cells was added to a compliant microporous tube made of segmented polyurethane. The compliance of the tube was close to that of the human artery [the stiffness parameter (β) = 57.2 (n = 5, SD < 5%)]. The luminal surface of the tube was fully covered with the cells by preincubation for two days in the presence of vascular endothelial growth factor (VEGF). After 2 days of additional incubation without VEGF under static conditions, layering of the grown cells, mostly smooth muscle actin (SMA)-positive cells, was observed only on the luminal surface of the tube. The cells were flat, polygonal, and randomly oriented. On the other hand, after a 2-day incubation under a weak pulsatile flow simulating the human venous systems [wall shear stress (WSS) from -0.98 to 2.2 dyn/cm2; circumferential strain (CS) 4.6-9.6 × 10 4 dyn/cm2] without VEGF, cells in the superficial layer were regularly oriented in the direction of the pulsatial flow. The oriented cells exhibited endothelial-like appearance, indicating that they were platelet endothelial cell adhesion molecule 1 (PECAM1)-positive. In addition, the cells growing into the interstices in the deeper layer showed smooth muscle-like appearance, indicating that they were SMA-positive. Differentiation to two different cell types and segregation of incorporated ES cells may be simultaneously encouraged by the combination of WSS and CS. It is expected that the monobloc building of hierarchically structured hybrid vascular prostheses composed of several vascular wall cell types is possible by physically synchronized differentiation of ES cells.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalJournal of Artificial Organs
Issue number2
Publication statusPublished - 2005 Aug
Externally publishedYes


  • Artificial vascular graft
  • Embryonic stem cell
  • Physical differentiation
  • Pulsatile flow
  • Vascular cell

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering
  • Cardiology and Cardiovascular Medicine


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