Acta Pharmacologica Sinica (2009) 30: 530-536; doi: 10.1038/aps.2009.40

Acta Pharmacologica Sinica (2009) 30: 530-536; doi: 10.1038/aps.2009.40

Original Article

Response of mesenchymal stem cells to shear stress in tissue-engineered vascular grafts

Jian-de DONG¹, Yong-quan GU¹, Chun-min LI¹, Chun-ren WANG², Zeng-guo FENG³, Rong-xin QIU³, Bing CHEN¹, Jian-xin LI¹, Shu-wen ZHANG⁴, Zhong-gao WANG¹, Jian ZHANG^1,*

¹Department of Vascular Surgery, Xuanwu Hospital and the Institute of Vascular Surgery, Capital University of Medical Sciences, Beijing 100053, China; ²National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100037, China; ³School of Materials Science & Engineering, Beijing Institute of Technology, Beijing 100081, China; ⁴Laboratory of Regenerative Medicine, Xuanwu Hospital and the Institute of Vascular Surgery, Capital University of Medical Sciences, Beijing 100053, China

Aim: Recent studies have demonstrated that mesenchymal stem cells (MSCs) can differentiate into endothelial cells. The effect of shear stress on MSC differentiation is incompletely understood, and most studies have been based on two-dimensional systems. We used a model of tissue-engineered vascular grafts (TEVGs) to investigate the effects of shear stress on MSC differentiation.

Methods: MSCs were isolated from canine bone marrow. The TEVG was constructed by seeding MSCs onto poly-ε-caprolactone and lactic acid (PCLA) scaffolds and subjecting them to shear stress provided by a pulsatile bioreactor for four days (two days at 1 dyne/cm² to 15 dyne/cm² and two days at 15 dyne/cm²).

Results: Shear stress significantly increased the expression of endothelial cell markers, such as platelet-endothelial cell adhesion molecule-1 (PECAM-1), VE-cadherin, and CD34, at both the mRNA and protein levels as compared with static control cells. Protein levels of alpha-smooth muscle actin (α-SMA) and calponin were substantially reduced in shear stress-cultured cells. There was no significant change in the expression of α-SMA, smooth muscle myosin heavy chain (SMMHC) or calponin at the mRNA level.

Conclusion: Shear stress upregulated the expression of endothelial cell-related markers and downregulated smooth muscle-related markers in canine MSCs. This study may serve as a basis for further investigation of the effects of shear stress on MSC differentiation in TEVGs.

Keywords: mesenchymal stem cells; shear stress; endothelial cells; differentiation; platelet-endothelial cell adhesion molecule-1; vWF; VE-cadherin; α-smooth muscle actin; calponin

We are grateful to Dr Ye-qing CUI, Dr Cui-fei YE, and Dr Xue-jing SUN for their technical assistance and advice. We also thank David CUSHLEY for his critical editing of the paper (International Science Editing Compuscript Ltd, Co Clare, Republic of Ireland ). This study was funded by the National High Technology Research and Development Program (? 863?/st1:chmetcnv> program) of China (No 2006AA 02A 134).

* Correspondence to Prof Jian ZHANG
Emal dongjiande99200@126.com
Received 2008-02-06 Accepted 2009-03-17

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