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

Institute of Neuroscience and Psychology College of Medical Veterinary and Life Sciences University of Glasgow Glasgow G12 8QQ UK

Laboratory for Human Neurophysiology and Genetics South Australian Health and Medical Research Institute Mind and Brain Adelaide South Australia Australia

Laboratory of Genetics The Salk Institute for Biological Studies La Jolla CA 92037 USA

Neuroregeneration Laboratory Department of Anesthesiology University of California San Diego La Jolla CA 92037 USA

Vector Development Core Laboratory UCSD La Jolla CA 92093 USA

Citace poskytuje Crossref.org

Expandable Sendai-Virus-Reprogrammed Human iPSC-Neuronal Precursors: In Vivo Post-Grafting Safety Characterization in Rats and Adult Pig

Derivation of Sendai-Virus-Reprogrammed Human iPSCs-Neuronal Precursors: In Vitro and In Vivo Post-grafting Safety Characterization

A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors