3,2 '-Dihydroxyflavone-Treated Pluripotent Stem Cells Show Enhanced Proliferation, Pluripotency Marker Expression, and Neuroprotective Properties
- Authors
- Han, Dawoon; Kim, Han Jun; Choi, Hye Yeon; Kim, BongWoo; Yang, Gwangmo; Han, Jihae; Dayem, Ahmed Abdal; Lee, Hye-Rim; Kim, Jin Hoi; Lee, Kyung-Mi; Jeong, Kyu-Shik; Do, Sun Hee; Cho, Ssang-Goo
- Issue Date
- 2015
- Publisher
- SAGE PUBLICATIONS INC
- Keywords
- 3,2 ' -Dihydroxyflavone; Pluripotent stem cell; Self-renewal; Peripheral nerve injury model; Neuroprotective property
- Citation
- CELL TRANSPLANTATION, v.24, no.8, pp.1511 - 1532
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL TRANSPLANTATION
- Volume
- 24
- Number
- 8
- Start Page
- 1511
- End Page
- 1532
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/96123
- DOI
- 10.3727/096368914X683511
- ISSN
- 0963-6897
- Abstract
- Efficient maintenance of the undifferentiated status of embryonic stem cells (ESCs) may be important for preparation of high-quality cell sources that can be successfully used for stem cell research and therapy. Here we tried to identify a compound that can enhance the quality of pluripotent stem cells. Treatment of ESCs and induced pluripotent stem cells (iPSCs) with 3,2'-dihydroxyflavone (3,2'-DHF) led to increases in cell growth, colony formation, and cell proliferation. Treatment with 3,2'-DHF resulted in high expression of pluripotency markers (OCT4, SOX2, and NANOG) and significant activation (STAT3 and AKT) or suppression (GSK3 beta and ERK) of self-renewal-related kinases. 3,2'-DHF-treated high-quality pluripotent stem cells also showed enhanced differentiation potential. In particular, treatment of iPSCs with 3,2'-DHF led to elevated expression of ectodermal differentiation markers and improved differentiation into fully matured neurons. Next, we investigated the in vivo effect of 3,2'-DHF-pretreated iPSCs (3,2'-DHF iPSCs) in a peripheral nerve injury model and found that transplantation of 3,2'-DHF iPSCs resulted in more efficient axonal regeneration and functional recovery than in controls. Upon histopathological and gene expression analyses, we found that transplantation of 3,2'-DHF iPSCs stimulated expression of cytokines, such as TNF-alpha, in the early phase of injury and successfully reduced convalescence time of the injured peripheral nerve, showing an effective neuroprotective property. Taken together, our data suggest that 3,2'-DHF can be used for more efficient maintenance of pluripotent stem cells as well as for further applications in stem cell research and therapy.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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