title: Ectopic pregnancy-derived human trophoblastic stem cells regenerate dopaminergic nigrostriatal pathway to treat parkinsonian rats.
abstract: BACKGROUND
  Stem cell therapy is a potential strategy to treat patients with Parkinson's disease (PD); however, several practical limitations remain. As such, finding the appropriate stem cell remains the primary issue in regenerative medicine today. We isolated a pre-placental pluripotent stem cell from the chorionic villi of women with early tubal ectopic pregnancies. Our objectives in this study were (i) to identify the characteristics of hTS cells as a potential cell source for therapy; and (ii) to test if hTS cells can be used as a potential therapeutic strategy for PD.
  
  
  RESULTS
  hTS cells expressed gene markers of both the trophectoderm (TE) and the inner cell mass (ICM). hTS cells exhibited genetic and biological characteristics similar to that of hES cells, yet genetically distinct from placenta-derived mesenchymal stem cells. All-trans retinoic acid (RA) efficiently induced hTS cells into trophoblast neural stem cells (tNSCs) in 1-day. Overexpression of transcription factor Nanog was possibly achieved through a RA-induced non-genomic c-Src/Stat3/Nanog signaling pathway mediated by the subcellular c-Src mRNA localization for the maintenance of pluripotency in tNSCs. tNSC transplantation into the lesioned striatum of acute and chronic PD rats not only improved behavioral deficits but also regenerated dopaminergic neurons in the nigrostriatal pathway, evidenced by immunofluorescent and immunohistological analyses at 18-weeks. Furthermore, tNSCs showed immunological advantages for the application in regenerative medicine.
  
  
  CONCLUSIONS
  We successfully isolated and characterized the unique ectopic pregnancy-derived hTS cells. hTS cells are pluripotent stem cells that can be efficiently induced to tNSCs with positive results in PD rat models. Our data suggest that the hTS cell is a dynamic stem cell platform that is potentially suitable for use in disease models, drug discovery, and cell therapy such as PD.
authors.affiliation: Department of Obstetrics and Gynecology and Center of Excellence for Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Tony Tung-Yin
authors.initials: TT
authors.lastname: Lee
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.forename: Tsung-Hsun
authors.initials: TH
authors.lastname: Hsieh
authors.forename: Jia-Jin Jason
authors.initials: JJ
authors.lastname: Chen
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Wang
authors.forename: Mi-Chun
authors.initials: MC
authors.lastname: Kao
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
authors.forename: Sher
authors.initials: S
authors.lastname: Singh
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.forename: Jau-Nan
authors.initials: JN
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016678:Genome; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000473:pathology*; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D053605:Leukemia Inhibitory Factor; D014212:Tretinoin; D004298:Dopamine