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3,2'-Dihydroxyflavone-Treated Pluripotent Stem Cells Show Enhanced Proliferation, Pluripotency Marker Expression, and Neuroprotective Properties.

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 (GSK3β 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-α, 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.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Han D,Kim HJ,Choi HY,Kim B,Yang G,Han J,Dayem AA,Lee HR,Kim JH,Lee KM,Jeong KS,Do SH,Cho SG

doi

10.3727/096368914X683511

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1511-32

issue

eissn

0963-6897

issn

1555-3892

pii

content-CT-1156_Han

journal_volume

pub_type

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3,2'-Dihydroxyflavone-Treated Pluripotent Stem Cells Show Enhanced Proliferation, Pluripotency Marker Expression, and Neuroprotective Properties.