Mol. Cells 2018; 41(6): 582~590  https://doi.org/10.14348/molcells.2018.0011
Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities
Yeon-Ju Kim1, Seung Taek Ji1, Da Yeon Kim1, Seok Yun Jung1, Songhwa Kang1, Ji Hye Park1,
Woong Bi Jang1, Jisoo Yun1,2, Jongseong Ha1,2, Dong Hyung Lee3, and Sang-Mo Kwon1,2,4,*
1Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine,
Pusan National University, Yangsan 50612, Korea, 2Convergence Stem Cell Research Center, Pusan National University,
Yangsan 50612, Korea, 3Department of Obstetrics and Gynecology, Biomedical Research Institute, Pusan National University
School of Medicine, Busan 46241, Korea, 4Research Institute of Convergence Biomedical Science and Technology, Pusan National
University Yangsan Hospital, Yangsan 50612, Korea
*Correspondence: smkwon323@pusan.ac.kr
Received January 5, 2018; Revised April 19, 2018; Accepted April 30, 2018.; Published online June 12, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.
Keywords: cell priming, endothelial progenitor cells, ischemic diseases, vascular repair


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30 June 2018 Volume 41,
Number 6, pp. 495~611

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