Response of mesenchymal stem cells to shear stress in tissue-engineered vascular grafts.
OBJECTIVE
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-epsilon-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/cm(2) to 15 dyne/cm(2) and two days at 15 dyne/cm(2)).


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 (alpha-SMA) and calponin were substantially reduced in shear stress-cultured cells. There was no significant change in the expression of alpha-SMA, smooth muscle myosin heavy chain (SMMHC) or calponin at the mRNA level.


CONCLUSIONS
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.
Dong
Jian-de
JD
Department of Vascular Surgery, Xuanwu Hospital and the Institute of Vascular Surgery, Capital University of Medical Sciences, Beijing, China. dongjiande99200@126.com
Gu
Yong-quan
YQ
Li
Chun-min
CM
Wang
Chun-ren
CR
Feng
Zeng-guo
ZG
Qiu
Rong-xin
RX
Chen
Bing
B
Li
Jian-xin
JX
Zhang
Shu-wen
SW
Wang
Zhong-gao
ZG
Zhang
Jian
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001807:Blood Vessel Prosthesis; D016026:Bone Marrow Transplantation; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004285:Dogs; D018960:Hyaluronan Receptors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008953:Models, Anatomic; D012313:RNA / Q000378:metabolism; D013314:Stress, Mechanical; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D000096985:Calponins
D000199:Actins; D018952:Antigens, CD34; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D018960:Hyaluronan Receptors; D008840:Microfilament Proteins; D012313:RNA; D000096985:Calponins