title: Pigment epithelium-derived factor secreted from retinal pigment epithelium facilitates apoptotic cell death of iPSC.
abstract: We show that pigment epithelium-derived factor (PEDF), which is secreted from primary or iPSC-derived retinal pigment epithelium (RPE), dramatically inhibits the growth of iPSCs. PEDF is detected abundantly in culture supernatants of primary or iPSC-derived RPE. Apoptotic cell death is induced in iPSC when co-cultured with RPE, a process that is significantly blocked by addition of antibody against PEDF. Indeed, addition of recombinant PEDF to the iPSC cell culture induces apoptotic cell death in iPSCs, but the expression of pluripotency related-genes is maintained, suggesting that PEDF causes cell death, not differentiation, of iPSCs. To recapitulate this event in vivo, we examined tumor formation in NOG mice after subcutaneous injection of iPSCs with or without an iPSC-derived RPE sheet (2.5 × 10(5) RPE cells). We observed that the tumor forming potential of iPSCs was significantly suppressed by simultaneous transplantation with an iPSC-derived RPE sheet.
authors.affiliation: Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Hoshimi
authors.initials: H
authors.lastname: Kanemura
authors.forename: Masahiro J
authors.initials: MJ
authors.lastname: Go
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishishita
authors.forename: Noriko
authors.initials: N
authors.lastname: Sakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamao
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sato
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shin
authors.initials: S
authors.lastname: Kawamata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005136:Eye Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D015843:Serpins / Q000378:metabolism*; D019745:cis-trans-Isomerases / Q000378:metabolism*; D000099178:Retinoid Isomerohydrolase; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; D000099174:Pigment Epithelium-Derived Factor
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