title: 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.
authors.affiliation: Department of Animal Biotechnology, Animal Resources Research Center, and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Gwangjin-Gu, Seoul, Republic of Korea.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Han
authors.forename: Han Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hye Yeon
authors.initials: HY
authors.lastname: Choi
authors.forename: BongWoo
authors.initials: B
authors.lastname: Kim
authors.forename: Gwangmo
authors.initials: G
authors.lastname: Yang
authors.forename: Jihae
authors.initials: J
authors.lastname: Han
authors.forename: Ahmed Abdal
authors.initials: AA
authors.lastname: Dayem
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Jin Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Do
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation; D008297:Male; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D020426:Sciatic Neuropathy / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C526335:3,2'-dihydroxyflavone; D005419:Flavonoids; D014157:Transcription Factors