Expandable Sendai-Virus-Reprogrammed Human iPSC-Neuronal Precursors: In Vivo Post-Grafting Safety Characterization in Rats and Adult Pig

可扩展仙台病毒重编程的人类 iPSC 神经元前体:大鼠和成年猪体内移植后安全性表征

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作者:Yoshiomi Kobayashi, Michiko Shigyo, Oleksandr Platoshyn, Silvia Marsala, Tomohisa Kato Jr, Naoki Takamura, Kenji Yoshida, Akiyoshi Kishino, Mariana Bravo-Hernandez, Stefan Juhas, Jana Juhasova, Hana Studenovska, Vladimir Proks, Shawn P Driscoll, Thomas D Glenn, Samuel L Pfaff, Joseph D Ciacci, Marti

Abstract

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

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