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.