Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites.
The mobilization and homing of endothelial progenitor cells (EPCs) are critical to the development of an antithrombotic cardiovascular prosthesis. Polyurethane (PU) with superior elasticity may provide a mechanical environment resembling that of the natural vascular tissues. The topographical cues of PU were maximized by making nanocomposites with a small amount of gold nanoparticles (AuNPs). The nanocomposites of PU-AuNPs ("PU-Au") with a favorable response of endothelial cells were previously established. In the current study, the effect of PU and PU-Au nanocomposites on the behavior of human peripheral blood EPCs was investigated in vitro and in vivo. It was found that PU-Au promoted EPCs to become differentiated endothelial cells in vitro, confirmed by the increased expressions of CD31 and VEGF-R2 surface markers. The increased maturation of EPCs was significantly more remarkable on PU-Au, probably through the stromal derived factor 1α (SDF-1α)/CXCR4 signaling pathway. In vivo experiments showed that EPCs seeded on PU-Au coated catheters effectively reduced thrombosis by differentiation into endothelial cells. Surface endothelialization with CD31 and CD34 expression as well as intimal formation with α-SMA expression was significantly accelerated in the group receiving EPC-seeded PU-Au catheters. Moreover, the analysis of collagen deposition revealed a reduction of fibrosis in the group receiving EPC-seeded PU-Au catheters as compared to the other groups. These results suggest that EPCs engineered with a proper elastic substrate may provide unique endothelialization and antithrombogenic properties that benefit vascular tissue regeneration.
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, ROC.
Huey-Shan
HS
Hung
Department of Surgery, Fong-Yuan Hospital Department of Health Executive Yuan, Taichung, Taiwan, ROC.
Yi-Chun
YC
Yang
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Yu-Chun
YC
Lin
Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, ROC; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ROC; China Medical University Beigang Hospital, Yunlin, Taiwan, ROC.
Shinn-Zong
SZ
Lin
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC.
Wei-Chien
WC
Kao
Blood Bank, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Hsien-Hsu
HH
Hsieh
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, ROC.
Mei-Yun
MY
Chu
Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, ROC; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ROC.
Ru-Huei
RH
Fu
Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, ROC; Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan, ROC. Electronic address: shhsu@ntu.edu.tw.
Shan-hui
SH
Hsu
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D053761:Nanocomposites / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011140:Polyurethanes / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties
C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D005343:Fibrinolytic Agents; D011140:Polyurethanes; D019718:Receptors, CXCR4; D006046:Gold; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
Endothelial progenitor cells (EPCs); Gold nanoparticles (AuNPs); Polyurethane; Vascular grafts