Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs

Jan Strnadel, Cassiano Carromeu, Cedric Bardy, Michael Navarro, Oleksandr Platoshyn, Andreas N. Glud, Silvia Marsala, Jozef Kafka, Atsushi Miyanohara, Tomohisa Kato Jr, Takahiro Tadokoro, Michael P. Hefferan, Kota Kamizato, Tetsuya Yoshizumi, Stefan Juhas, Jana Juhasova, Chak Sum Ho, Taba Kheradmand, Pei Xi Chen, Dasa BohaciakovaMarian Hruska-Plochan, Andrew J. Todd, Shawn P. Driscoll, Thomas D. Glenn, Samuel L. Pfaff, Jiri Klima, Joseph Ciacci, Eric Curtis, Fred H. Gage, Jack Bui, Kazuhiko Yamada, Alysson R. Muotri, Martin Marsala

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbereaam6651
Number of pages15
JournalScience Translational Medicine
Volume10
Issue number440
DOIs
Publication statusPublished - 9 May 2018
Externally publishedYes

Keywords

  • spinal grafting
  • autologous cells
  • stem cells
  • spinal cord injury
  • NPC transplants
  • syngeneic
  • allogeneic
  • iPSC-derived neural precursors

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    Strnadel, J., Carromeu, C., Bardy, C., Navarro, M., Platoshyn, O., Glud, A. N., Marsala, S., Kafka, J., Miyanohara, A., Jr, T. K., Tadokoro, T., Hefferan, M. P., Kamizato, K., Yoshizumi, T., Juhas, S., Juhasova, J., Ho, C. S., Kheradmand, T., Chen, P. X., ... Marsala, M. (2018). Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs. Science Translational Medicine, 10(440), [eaam6651]. https://doi.org/10.1126/scitranslmed.aam6651