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

Strnadel, J. et al. (2018) Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs. Science Translational Medicine, 10(440), eaam6651. (doi: 10.1126/scitranslmed.aam6651) (PMID:29743351)

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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.

Item Type:Articles
Additional Information:J.S. and M.H.-P. were partially supported by the California Institute for Regenerative Medicine (CIRM) Comprehensive Grant and ImmunologyTransplantation grant (RC1-00131-1; RM1-01720; M.M. and J.B.) and Sanford Consortium for Regenerative Medicine (SANPORC; M.M.). J.S. was partially supported by the Czech Academy of Sciences (Institutional Research Plan, Institute of Animal Physiology and Genetics no. AV0Z50450515). University of California, San Diego (UCSD) Neuroscience Microscopy Facility was supported by the NIH (NS047101). S.J., J.J., and J.K. were partially supported by the National Sustainability Program I, project number LO1609 (Czech Ministry of Education, Youth and Sports), and RVO: 67985904. A.M. was partially supported by NIH (PO1-HL066941). J.B. is also supported by NIH grants (CA157885 and CA128893). A.R.M. is supported by grants from the CIRM TR2-01814 and TR4-06747, the NIH through R21MH107771, R01MH094753, and U19MH107367, and a NARSAD (National Alliance for Research on Schizophrenia and Depression) Independent Investigator grant to A.R.M. M.M. was supported by NIH (R01OD018272).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Todd, Professor Andrew
Authors: Strnadel, J., Carromeu, C., Bardy, C., Navarro, M., Platoshyn, O., Glud, A. N., Marsala, S., Kafka, J., Miyanohara, A., Kato, T., Tadokoro, T., Hefferan, M. P., Kamizato, K., Yoshizumi, T., Juhas, S., Juhasova, J., Ho, C.-S., Kheradmand, T., Chen, P., Bohaciakova, D., Hruska-Plochan, M., Todd, A. J., Driscoll, S. P., Glenn, T. D., Pfaff, S. L., Klima, J., Ciacci, J., Curtis, E., Gage, F. H., Bui, J., Yamada, K., Muotri, A. R., and Marsala, M.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Science Translational Medicine
Publisher:American Association for the Advancement of Science
ISSN:1946-6234
ISSN (Online):1946-6242
Copyright Holders:Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
First Published:First published in Science Translational Medicine 10(440):eaam6651
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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