Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity
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Murine and human iPSC-NS/PCs (induced pluripotent stem cell-derived neural stem/progenitor cells) promote functional recovery following transplantation into the injured spinal cord in rodents. However, for clinical applicability, it is critical to obtain proof of the concept regarding the efficacy of grafted human iPSC-NS/PCs (hiPSC-NS/PCs) for the repair of spinal cord injury (SCI) in a non-human primate model. This study used a pre-evaluated "safe" hiPSC-NS/PC clone and an adult common marmoset (Callithrix jacchus) model of contusive SCI. SCI was induced at the fifth cervical level (C5), followed by transplantation of hiPSC-NS/PCs at 9 days after injury. Behavioral analyses were performed from the time of the initial injury until 12 weeks after SCI. Grafted hiPSC-NS/PCs survived and differentiated into all three neural lineages. Furthermore, transplantation of hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, and prevented the demyelination after SCI compared with that in vehicle control animals. Notably, no tumor formation occurred for at least 12 weeks after transplantation. Quantitative RT-PCR showed that mRNA expression levels of human neurotrophic factors were significantly higher in cultured hiPSC-NS/PCs than in human dermal fibroblasts (hDFs). Finally, behavioral tests showed that hiPSC-NS/PCs promoted functional recovery after SCI in the common marmoset. Taken together, these results indicate that pre-evaluated safe hiPSC-NS/PCs are a potential source of cells for the treatment of SCI in the clinic.
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In a mouse spinal cord injury model, transplanting neural stem/progenitor cells made from human iPSCs was reported to promote ongoing motor recovery.
“Similarly, transplantation of neural stem or progenitor cells derived from human induced pluripotent stem cells (iPSCs) in a mouse of model of spinal cord injury was reported to stimulate continual motor function recovery148,149.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [148]
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References 72 · Cited by 315
- Authors
- Kobayashi, Y., Okada, Y., Itakura, G., Iwai, H., Nishimura, S., Yasuda, A., Nori, S., Hikishima, K., Konomi, T., Fujiyoshi, K., Tsuji, O., Toyama, Y., Yamanaka, S., Nakamura, M., & Okano, H.
- Affiliations
- Keio University (JP)
- Murayama Medical Center (JP)
- Center for iPS Cell Research and Application, Kyoto University (JP)
- Corresponding author
- Nakamura, Masaya
- Okano, Hideyuki
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-12-27
- Volume
- 7
- Issue
- 12
- Pages
- e52787
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3531369
- OpenAlex
- W1984257202
- Cited by
- 315
- References
- 72
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 17 · 2023: 15 · 2022: 23 · 2021: 27 · 2020: 23 · 2019: 33 · 2018: 36 · 2017: 28 · 2016: 27 · 2015: 25 · 2014: 35 · 2013: 6 · 2012: 1
- FWCI
- 15.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- California Institute for Regenerative Medicine
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (23650194, 23689017)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- spinal cord injury, Callithrix jacchus, spinal cord contusion, functional recovery, tumorigenicity, axon regeneration, angiogenesis, demyelination, neurotrophic factors, cell transplantation, nonhuman primate model
- MeSH terms
- Animals, Callithrix, Cell Differentiation, Cell Survival, Cell Transformation, Neoplastic, Cells, Cultured, Cicatrix, Demyelinating Diseases, Female, Humans, Locomotion, Motor Neurons, Nerve Growth Factors, Nerve Regeneration, Spinal Cord, Spinal Cord Injuries, Calcitonin Gene-Related Peptide, Microglia, Hand Strength, Neovascularization, Physiologic, Recovery of Function, Stem Cell Transplantation, Induced Pluripotent Stem Cells, Neural Stem Cells
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