1H-pyrrole-2,5-dione-based small molecule-induced generation ofmesenchymal stem cell-derived functional endothelial cells thatfacilitate rapid endothelialization after vascular injury

Collection with item attached
2015
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473407.do
DOI
10.1186/s13287-015-0170-6
Title
1H-pyrrole-2,5-dione-based small molecule-induced generation ofmesenchymal stem cell-derived functional endothelial cells thatfacilitate rapid endothelialization after vascular injury
Description
This study was supported by a Korea Science and Engineering Foundationgrant funded by the Korean government (MEST) (NRF-2011-0019243,NRF-2011-0019254, NRF-2015M3A9E6029519, and NFR-2015M3A9E6029407) and agrant from the Korea Health 21 R&D Project, Ministry of Health &Welfare, Republic of Korea (A120478).
abstract
Introduction: Despite the success of interventional processes such as drug-eluting stents, complete prevention of restenosis is still hindered by impaired or delayed endothelialization or both. Here, we report that 1H-pyrrole-2,5-dione-based small molecule-generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) facilitated rapid transmural coverage of injured blood vessels.
Methods: Small molecules that induced CD31 expression were screened by principal component analysis (PCA). Rat mesenchymal stem cells (MSCs) were treated with selected small molecules for up to 16 days, and the expression levels of CD90 and CD31 were examined by immunocytochemistry. In vitro functional assays of MDFECs, including tube formation assays and nitric oxide production assays, were performed. After MDFECs (intravenous, 3x10(6) cells per animal) were injected into balloon-injured rats, neointima formation was monitored for up to 21 days. The endothelial coverage of denuded blood vessels was evaluated by Evans Blue staining. The functionality of repaired blood vessels was evaluated by measuring vasorelaxation and hemodynamic changes. Additionally, derivatives of the selected small molecules were examined for their ability to induce endothelial markers.
Results: PCA indicated that 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione effectively induced MDFECs. MDFECs inhibited the neointima formation of denuded blood vessels by facilitating more rapid endothelialization. Further examination indicated that derivatives with a 1H-pyrrole-2,5-dione moiety are important for initiating the endothelial cell differentiation of MSCs.
Conclusions: Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis.
provenance
Made available in Cube on 2018-09-28T10:18:40Z (GMT). No. of bitstreams: 0
language
English
author
Song, Byeong-Wook
Kim, Il-Kwon
Lee, Seahyoung
Choi, Eunhyun
Ham, Onju
Lee, Se-Yeon
Lee, Chang Yeon
Park, Jun-Hee
Lee, Jiyun
Seo, Hyang-Hee
Chang, Woochul
Yoon, Cheesoon
Hwang, Ki-Chul
accessioned
2018-09-28T10:18:40Z
available
2018-09-28T10:18:40Z
issued
2015
citation
STEM CELL RESEARCH & THERAPY(6)
issn
1757-6512
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473407.do
Funder
미래창조과학부
Funding Program
바이오·의료기술개발
Project ID
1711025760
Jurisdiction
Rep.of Korea
Project Name
Identification of small molecules for specific differentiation of mesenchymal stem cells into specific mesoderm cells and function research for tissue regeneration
rights
openAccess
type
article


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