Pigment Epithelium-Derived Factor Secreted from Retinal Pigment Epithelium Facilitates Apoptotic Cell Death of iPSC
نویسندگان
چکیده
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.
منابع مشابه
Morphological changes in injured retinal pigment epithelium and photoreceptor cells after transplantation of stem cells into subretinal space
Introduction: Degenerative retinal diseases are main cause of irreversible blindness. Stem cells therapy is a promising way in these diseases. Therefore, mesenchymal stem cells because of its safety can produce degenerated cells and can play important role in treatment. The aim of this study was to examine morphological changes in injured retinal pigment epithelium (RPE) and photoreceptor cells...
متن کاملHistochemical study of retinal photoreceptors development during pre- and postnatal period and their association with retinal pigment epithelium
Objective(s):The aim of this study was to evaluate distribution and changes of glycoconjugates of retinal photoreceptors during both pre- and postnatal development. Materials and Methods: Tissue sections from days 15 to 20 of Wistar rat embryos and 1 to 12 postnatal days of rat newborns including developing eye were prepared for lectinhistochemistry technique. Horseradish peroxidase (HRP)-label...
متن کاملNeural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study
Background: Pigment epithelium-derived factor (PEDF) is regarded as a multifunctional protein possessing neurotrophic and neuroprotective properties. PEDF has a very short half-life, and it would require multiple injections to maintain a therapeutically relevant level without a delivery system. However, multiple injections are prone to cause local damage or infection. To overcome this, we chose...
متن کاملPigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration
AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults...
متن کاملIn Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications
: Induced pluripotent stem cells (iPSCs) can be efficiently differentiated into retinal pigment epithelium (RPE), offering the possibility of autologous cell replacement therapy for retinal degeneration stemming from RPE loss. The generation and maintenance of epithelial apical-basolateral polarity is fundamental for iPSC-derived RPE (iPSC-RPE) to recapitulate native RPE structure and function....
متن کامل