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Sci Transl Med. 2018 May 9;10(440). pii: eaam6651. doi: 10.1126/scitranslmed.aam6651.

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

Author information

1
Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
2
Biomedical Center Martin, Department of Molecular Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia.
3
Department of Pediatrics, UCSD, La Jolla, CA 92037, USA.
4
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
5
Laboratory for Human Neurophysiology and Genetics, South Australian Health & Medical Research Institute (SAHMRI) Mind and Brain, Adelaide, South Australia, Australia.
6
Vector Development Core Laboratory, UCSD, La Jolla, CA 92093, USA.
7
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
8
Institute of Animal Physiology and Genetics, v.v.i., The Czech Academy of Sciences, Liběchov, Czech Republic.
9
Histocompatibility Laboratory, Gift of Life Michigan, Ann Arbor, MI 48108, USA.
10
Department of Histology and Embryology, Masaryk University, Brno, Czech Republic.
11
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
12
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
13
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
14
Department of Neurosurgery, UCSD, La Jolla, CA 92103, USA.
15
Department of Pathology, UCSD, La Jolla, CA 92093, USA.
16
Columbia University Medical Center Campus, New York, NY 10032, USA.
17
Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. mmarsala@ucsd.edu.
18
Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia.

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.

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