PMID- 24032550
OWN - NLM
STAT- MEDLINE
DCOM- 20140129
LR  - 20220409
IS  - 1557-7430 (Electronic)
IS  - 1044-5498 (Print)
IS  - 1044-5498 (Linking)
VI  - 32
IP  - 12
DP  - 2013 Dec
TI  - Induction of estrogen-sensitive epithelial cells derived from human-induced 
      pluripotent stem cells to repair ovarian function in a chemotherapy-induced mouse 
      model of premature ovarian failure.
PG  - 685-98
LID - 10.1089/dna.2013.2032 [doi]
AB  - The incidence of premature ovarian failure (POF), a condition causing amenorrhea 
      and hypergonadotropic hypoestrogenism in women before the age of 40, has been 
      increasing in recent years. As an irreversible pathological change, improved 
      treatment strategies for this disease are urgently needed. In this study, a type 
      of microRNA (miR-17-3p) was used to guide the differentiation of human-induced 
      pluripotent stem (iPS) cells into hormone-sensitive ovarian epithelial (OSE)-like 
      cells in vitro. To prevent their morphological transformation into 
      fibroblast-like cells, MiR-17-3p, a microRNA that suppresses vimentin expression, 
      was transfected into human iPS cells. Subsequently, these cells were successfully 
      induced into OSE-like cells in vitro after treatment with estrogen and cell 
      growth factors. Compared with controls, iPS cells transfected with miR-17-3p 
      expressed higher levels of epithelial markers (cytokeratin 7, AE1, AE3, and 
      E-cadherin) and estrogen receptors (ERalpha and ERbeta) while levels of mesenchymal 
      markers (fibronectin, vimentin, and N-cadherin) lowered after the induction. The 
      human iPS cell-derived OSE-like cells were then injected into 
      cyclophosphamide-induced POF model mice to determine their potential benefit as 
      grafts to repair ovarian tissues. The OSE-like cells survived within POF mouse 
      ovaries for at least 14 days in vivo. Compared with the negative controls, 
      expressions of cytokeratin 7 and ERbeta proteins were elevated while fibronectin and 
      vimentin levels in ovarian tissues were downregulated in the OSE-like cell 
      transplantation group. Moreover, the ovarian weight and plasma E2 level increased 
      over time in the transplantation with OSE-like cells, compared with control 
      groups. Hence, we can draw the conclusion that iPS cells can be induced to 
      differentiate into OSE-like cells in vitro.
FAU - Liu, Te
AU  - Liu T
AD  - 1 Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai 
      University of Traditional Chinese Medicine , Shanghai, China .
FAU - Qin, Wenxing
AU  - Qin W
FAU - Huang, Yongyi
AU  - Huang Y
FAU - Zhao, Yanhui
AU  - Zhao Y
FAU - Wang, Jiejun
AU  - Wang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130914
PL  - United States
TA  - DNA Cell Biol
JT  - DNA and cell biology
JID - 9004522
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Epithelial Cells/*cytology/*metabolism
MH  - Estrogen Receptor alpha/*metabolism/therapeutic use
MH  - Female
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*cytology
MH  - Mice
MH  - Organ Size
MH  - Polymerase Chain Reaction
MH  - *Primary Ovarian Insufficiency/chemically induced/therapy
PMC - PMC3864371
EDAT- 2013/09/17 06:00
MHDA- 2014/01/30 06:00
PMCR- 2014/12/01
CRDT- 2013/09/17 06:00
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/01/30 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 10.1089/dna.2013.2032 [pii]
AID - 10.1089/dna.2013.2032 [doi]
PST - ppublish
SO  - DNA Cell Biol. 2013 Dec;32(12):685-98. doi: 10.1089/dna.2013.2032. Epub 2013 Sep 
      14.