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

Strnadel, Jan
Author Strnadel, Jan ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA Biomedical Center Martin, Department of Molecular Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
Carromeu, Cassiano
Author Carromeu, Cassiano Department of Pediatrics, UCSD, La Jolla, CA 92037, USA
Bardy, Cedric
Author Bardy, Cedric ORCID Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA Laboratory for Human Neurophysiology and Genetics, South Australian Health & Medical Research Institute (SAHMRI) Mind and Brain, Adelaide, South Australia, Australia
Navarro, Michael
Author Navarro, Michael ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Platoshyn, Oleksandr
Author Platoshyn, Oleksandr Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Glud, Andreas N
Author Glud, Andreas N ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Marsala, Silvia
Author Marsala, Silvia ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Kafka, Jozef
Author Kafka, Jozef Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Miyanohara, Atsushi
Author Miyanohara, Atsushi Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA Vector Development Core Laboratory, UCSD, La Jolla, CA 92093, USA
Kato, Tomohisa Jr
Author Kato, Tomohisa Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Tadokoro, Takahiro
Author Tadokoro, Takahiro Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Hefferan, Michael P
Author Hefferan, Michael P Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Kamizato, Kota
Author Kamizato, Kota Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Yoshizumi, Tetsuya
Author Yoshizumi, Tetsuya ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Juhas, Stefan
Author Juhas, Stefan Institute of Animal Physiology and Genetics, v.v.i., The Czech Academy of Sciences, Liběchov, Czech Republic
Juhasova, Jana
Author Juhasova, Jana Institute of Animal Physiology and Genetics, v.v.i., The Czech Academy of Sciences, Liběchov, Czech Republic
Ho, Chak-Sum
Author Ho, Chak-Sum ORCID Histocompatibility Laboratory, Gift of Life Michigan, Ann Arbor, MI 48108, USA
Kheradmand, Taba
Author Kheradmand, Taba Histocompatibility Laboratory, Gift of Life Michigan, Ann Arbor, MI 48108, USA
Chen, PeiXi
Author Chen, PeiXi ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA
Bohaciakova, Dasa
Author Bohaciakova, Dasa ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA Department of Histology and Embryology, Masaryk University, Brno, Czech Republic
Hruska-Plochan, Marian
Author Hruska-Plochan, Marian ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Todd, Andrew J
Author Todd, Andrew J ORCID Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Driscoll, Shawn P
Author Driscoll, Shawn P Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Glenn, Thomas D
Author Glenn, Thomas D Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Pfaff, Samuel L
Author Pfaff, Samuel L ORCID Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Klima, Jiri
Author Klima, Jiri Institute of Animal Physiology and Genetics, v.v.i., The Czech Academy of Sciences, Liběchov, Czech Republic
Ciacci, Joseph
Author Ciacci, Joseph Department of Neurosurgery, UCSD, La Jolla, CA 92103, USA
Curtis, Eric
Author Curtis, Eric ORCID Department of Neurosurgery, UCSD, La Jolla, CA 92103, USA
Gage, Fred H
Author Gage, Fred H ORCID Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Bui, Jack
Author Bui, Jack ORCID Department of Pathology, UCSD, La Jolla, CA 92093, USA
Yamada, Kazuhiko
Author Yamada, Kazuhiko Columbia University Medical Center Campus, New York, NY 10032, USA
Muotri, Alysson R
Author Muotri, Alysson R ORCID Department of Pediatrics, UCSD, La Jolla, CA 92037, USA
Marsala, Martin
Author Marsala, Martin ORCID Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. mmarsala@ucsd.edu Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia

Science translational medicine. 2018 May 09 ; 10 (440) : .

Sci Transl Med
ISSN 1946-6242 | 1946-6234
Source

Language English Country United States Media print

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid29743351

Grant support
P01 HL066941 NHLBI NIH HHS - United States
R21 MH107771 NIMH NIH HHS - United States
R01 MH094753 NIMH NIH HHS - United States
U19 MH107367 NIMH NIH HHS - United States
R01 OD018272 NIH HHS - United States

PubMed 29743351
DOI 10.1126/scitranslmed.aam6651
PII: 10/440/eaam6651
Knihovny.cz E-resources

MeSH
Survival Analysis MeSH
Cell Differentiation MeSH
Chronic Disease MeSH
Fibroblasts cytology MeSH
Transplantation, Homologous MeSH
Immunity, Humoral MeSH
Immune Tolerance MeSH
Immunosuppression Therapy MeSH
Induced Pluripotent Stem Cells cytology MeSH
Rats MeSH
Skin cytology MeSH
Spinal Cord transplantation MeSH
Swine, Miniature MeSH
Neostriatum pathology MeSH
Neural Stem Cells cytology transplantation MeSH
Neurons cytology MeSH
Spinal Cord Injuries pathology therapy MeSH
Swine MeSH
Cellular Reprogramming MeSH
Gene Expression Regulation MeSH
Aging MeSH
Transplantation, Isogeneic MeSH
Animals MeSH
Check Tag
Rats MeSH
Animals MeSH
Publication type
Journal Article MeSH
Research Support, Non-U.S. Gov't MeSH
Research Support, N.I.H., Extramural MeSH

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.

Biomedical Center Martin Department of Molecular Medicine Jessenius Faculty of Medicine in Martin Comenius University in Bratislava 03601 Martin Slovakia

Center for iPS Cell Research and Application Kyoto University Kyoto Japan

Columbia University Medical Center Campus New York NY 10032 USA

Department of Histology and Embryology Masaryk University Brno Czech Republic

Department of Neurosurgery UCSD La Jolla CA 92103 USA

Department of Pathology UCSD La Jolla CA 92093 USA

Department of Pediatrics UCSD La Jolla CA 92037 USA

Gene Expression Laboratory and the Howard Hughes Medical Institute Salk Institute for Biological Studies La Jolla CA 92037 USA

Histocompatibility Laboratory Gift of Life Michigan Ann Arbor MI 48108 USA

Institute of Animal Physiology and Genetics v v i The Czech Academy of Sciences Liběchov Czech Republic

Institute of Molecular Life Sciences University of Zurich Winterthurerstrasse 190 8057 Zurich Switzerland

Institute of Neurobiology Slovak Academy of Sciences Kosice Slovakia