PT - JOURNAL ARTICLE AU - Strnadel, Jan AU - Carromeu, Cassiano AU - Bardy, Cedric AU - Navarro, Michael AU - Platoshyn, Oleksandr AU - Glud, Andreas N. AU - Marsala, Silvia AU - Kafka, Jozef AU - Miyanohara, Atsushi AU - Kato, Tomohisa AU - Tadokoro, Takahiro AU - Hefferan, Michael P. AU - Kamizato, Kota AU - Yoshizumi, Tetsuya AU - Juhas, Stefan AU - Juhasova, Jana AU - Ho, Chak-Sum AU - Kheradmand, Taba AU - Chen, PeiXi AU - Bohaciakova, Dasa AU - Hruska-Plochan, Marian AU - Todd, Andrew J. AU - Driscoll, Shawn P. AU - Glenn, Thomas D. AU - Pfaff, Samuel L. AU - Klima, Jiri AU - Ciacci, Joseph AU - Curtis, Eric AU - Gage, Fred H. AU - Bui, Jack AU - Yamada, Kazuhiko AU - Muotri, Alysson R. AU - Marsala, Martin TI - Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs AID - 10.1126/scitranslmed.aam6651 DP - 2018 May 09 TA - Science Translational Medicine PG - eaam6651 VI - 10 IP - 440 4099 - http://stm.sciencemag.org/content/10/440/eaam6651.short 4100 - http://stm.sciencemag.org/content/10/440/eaam6651.full AB - Neural precursor cells (NPCs) hold promise for treating spinal cord injury (SCI). Testing viability and engraftment properties of NPC transplants in large-animal models is necessary for understanding the clinical potential of this approach. In a new study, Strnadel et al. transplanted syngeneic and allogeneic induced pluripotent stem cell–derived NPCs (iPSC-NPCs) into the spinal cords of naïve pigs and animals with SCI. The transplanted cells showed a good safety profile, long-term survival, and differentiation into mature neurons and glial cells. Successful engraftment of allogeneic iPSC-NPCs required only temporary immunosuppression, an important consideration for the future clinical evaluation of iPSC-NPCs for treating SCI.The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)–mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.