Abstract
The generation of human induced pluripotent stem cells (hiPSC) from somatic cells has enabled the possibility to provide patient-specific hiPSC for cell-based therapy, drug discovery, and other translational applications. Two major obstacles in using hiPSC for clinical application reside in the risk of genomic modification when they are derived with viral transgenes and risk of teratoma formation if undifferentiated cells are engrafted. In this study, we report the generation of "footprint-free" hiPSC-derived astrocytes. These are efficiently generated, have anatomical and physiological characteristics of fully differentiated astrocytes, maintain homing characteristics typical of stem cells, and do not give rise to teratomas when engrafted in the brain. Astrocytes can be obtained in sufficient numbers, aliquoted, frozen, thawed, and used when needed. Our results show the feasibility of differentiating astrocytes from "footprint-free" iPSC. These are suitable for clinical cell-based therapies as they can be induced from patients' specific cells, do not require viral vectors, and are fully differentiated. "Footprint-free" hiPSC-derived astrocytes represent a new potential source for therapeutic use for cell-based therapy, including treatment of high-grade human gliomas, and drug discovery.