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 × 105 RPE cells). We observed that the tumor forming potential of iPSCs was significantly suppressed by simultaneous transplantation with an iPSC-derived RPE sheet.
Highlights
We show that pigment epithelium-derived factor (PEDF), which is secreted from primary or induced pluripotent stem cells (iPSC)-derived retinal pigment epithelium (RPE), dramatically inhibits the growth of iPSCs
We recently reported a method that was highly sensitive for the detection of residual iPSCs in iPSC-derived retinal pigment epithelium (RPE)
In an effort to establish a robust differentiation protocol for pluripotent stem cells into retinal pigment epithelium (RPE), the differentiation protocol shown in Figure 1A was used
Summary
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. Tumor formation from residual undifferentiated iPSCs or ESCs is an issue to be evaluated carefully in the transplantation of pluripotent stem cell-derived tissue products. This issue becomes more serious in the case of transplanting autologous iPSC-derived cells or tissues at sites lacking an immune barrier. We recently reported a method that was highly sensitive for the detection of residual iPSCs in iPSC-derived retinal pigment epithelium (RPE). It relied on qRT-PCR using primers for the LIN28A transcript[3].
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