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Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery
Open accessAbstract
Stem cell-based approaches to restore function after stroke through replacement of dead neurons require the generation of specific neuronal subtypes. Loss of neurons in the cerebral cortex is a major cause of stroke-induced neurological deficits in adult humans. Reprogramming of adult human somatic cells to induced pluripotent stem cells is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells can be converted to functional cortical neurons that survive and give rise to behavioural recovery after transplantation in the stroke-injured cerebral cortex is not known. We have generated progenitors in vitro, expressing specific cortical markers and giving rise to functional neurons, from long-term self-renewing neuroepithelial-like stem cells, produced from adult human fibroblast-derived induced pluripotent stem cells. At 2 months after transplantation into the stroke-damaged rat cortex, the cortically fated cells showed less proliferation and more efficient conversion to mature neurons with morphological and immunohistochemical characteristics of a cortical phenotype and higher axonal projection density as compared with non-fated cells. Pyramidal morphology and localization of the cells expressing the cortex-specific marker TBR1 in a certain layered pattern provided further evidence supporting the cortical phenotype of the fated, grafted cells, and electrophysiological recordings demonstrated their functionality. Both fated and non-fated cell-transplanted groups showed bilateral recovery of the impaired function in the stepping test compared with vehicle-injected animals. The behavioural improvement at this early time point was most likely not due to neuronal replacement and reconstruction of circuitry. At 5 months after stroke in immunocompromised rats, there was no tumour formation and the grafted cells exhibited electrophysiological properties of mature neurons with evidence of integration in host circuitry. Our findings show, for the first time, that human skin-derived induced pluripotent stem cells can be differentiated to cortical neuronal progenitors, which survive, differentiate to functional neurons and improve neurological outcome after intracortical implantation in a rat stroke model.
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“The transplantation of human PSC-derived cortical pyramidal neurons into the lesioned adult cortex has been shown to be promising (Espuny-Camacho et al., 2018, Tornero et al., 2013, Tornero et al., 2017)”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Tornero et al., 2013
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Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
Shi, Y., Kirwan, P., Smith, J., Robinson, H. P. C., & Livesey, F. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3041 · Cited by 813
Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis
Kuwabara, T., Hsieh, J., Muotri, A., Yeo, G., Warashina, M., Lie, D. C., Moore, L., Nakashima, K., Asashima, M., & Gage, F. H. (2009) · Nature Neuroscience · doi:10.1038/nn.2360 · Cited by 648
An intrinsic mechanism of corticogenesis from embryonic stem cells
Gaspard, N., Bouschet, T., Hourez, R., Dimidschstein, J., Naeije, G., van den Ameele, J., Espuny-Camacho, I., Herpoel, A., Passante, L., Schiffmann, S. N., et al. (2008) · Nature · doi:10.1038/nature07287 · Cited by 641
Olsson, M. A., Nikkhah, G., Bentlage, C., & Björklund, A. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03863.1995 · Cited by 625
Kelly, S., Bliss, T. M., Shah, A. K., Sun, G.-H., Ma, M., Foo, W. C., Masel, J., Yenari, M. A., Weissman, I. L., Uchida, N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404474101 · Cited by 624
A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction.
Chen, S. T., Hsu, C. Y., HOGAN, E. L., Maricq, H. R., & Balentine, J. D. (1986) · Stroke · doi:10.1161/01.str.17.4.738 · Cited by 594
Espuny-Camacho, I., Michelsen, K. A., Gall, D., Linaro, D., Hasche, A., Bonnefont, J., Bali, C., Orduz, D., Bilheu, A., Herpoel, A., et al. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.011 · Cited by 568
Modeling human cortical development in vitro using induced pluripotent stem cells
Mariani, J., Simonini, M. V., Palejev, D., Tomasini, L., Coppola, G., Szekely, A. M., Horvath, T. L., & Vaccarino, F. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202944109 · Cited by 526
Koch, P., Opitz, T., Steinbeck, J. A., Ladewig, J., & Brüstle, O. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808387106 · Cited by 508
Self-citationHargus, G., Cooper, O., Deleidi, M., Levy, A. E., Lee, K., Marlow, E. D., Yow, A., Soldner, F., Hockemeyer, D. F., Hallett, P. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010209107 · Cited by 480
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Lau, V. W., Platt, S. R., Stice, S. L., & West, F. D. (2015) · Springer eBooks · doi:10.1007/978-3-319-15063-5_10 · Cited by 1
Induced Pluripotent Stem Cells as a Cell-Based Therapeutic in Stroke
Hess, D. C., Fakhri, N., & West, F. D. (2015) · Springer eBooks · doi:10.1007/978-3-319-15063-5_9 · Cited by 1
Ischemic Stroke Pathophysiology and Cell Therapy
Ren, C., Han, R., Shi, J., & Ji, X. (2016) · Springer eBooks · doi:10.1007/978-981-10-2929-5_1 · Cited by 1
Sandvig, A., & Sandvig, I. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00630 · Cited by 1
Martínez-Curiel, R., Hajy, M., Tsupykov, O., Jansson, L., Avaliani, N., Tampé, J., Monni, E., Skibo, G. G., Lindvall, O., Palma-Tortosa, S., et al. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf049 · Cited by 1
Self-citationStem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors
Popa‐Wagner, A., & Napoli, M. D. (2017) · Springer series in translational stroke research · doi:10.1007/978-3-319-66679-2_3 · Cited by 1
Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies
Singh, P. (2018) · International Journal of Science Technology & Society · doi:10.18091/ijsts.4122 · Cited by 1
Stem Cell-Based Stroke Treatment
Alavian, F., & Ghasemi, S. (2019) · The Neuroscience Journal of Shefaye Khatam · doi:10.29252/shefa.8.1.99 · Cited by 1
The therapeutic potential of exogenous adult stem cells for the injured central nervous system
Smith, J. A., Braga, A., Hamel, R., Rutigliani, C., Yu, B., Peruzzotti‐Jametti, L., & Pluchino, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818084-6.00006-4 · Cited by 1
Current progress in brain organoid technology
Wei, P. A. N. G., YanTong, L. I. U., & Xiang, Y. (2022) · Scientia Sinica Vitae · doi:10.1360/ssv-2021-0278 · Cited by 1
Martínez-Curiel, R., Jansson, L., Tsupykov, O., Avaliani, N., Aretio-Medina, C., Hidalgo, I., Monni, E., Bengzon, J., Skibo, G. G., Lindvall, O., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.24.534133 · Cited by 1
Self-citationLi, Y., Liu, X., Wang, M., Li, L., Wang, X., Yin, R., Zhao, L., Zhao, J., Wen, X. H., Song, Q. W., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7950969/v1 · Cited by 1
Neurogenesis from Neural Stem Cells, Ependymal Cells and Fibroblasts
Devaraju, K. (2014) · Lund University Publications (Lund University)
Self-citationAvaliani, N. (2015) · Lund University Publications (Lund University)
Shen, F., & Su, H. (2017) · Translational medicine research · doi:10.1007/978-981-10-5804-2_20
Gene Modified Stem/Progenitor‐Cell Therapy for Ischemic Stroke
Li, Y., Yang, G., & Wang, Y. (2016) · doi:10.1002/9781119135449.ch18
Potential Mechanisms of Transplanted Cell-Mediated Recovery After Stroke
Wang, B. Z., Hui, A. C. F., & Jin, K. (2016) · Springer eBooks · doi:10.1007/978-981-10-2929-5_12
Yamashita, T., & Abe, K. (2017) · Springer eBooks · doi:10.1007/978-4-431-56059-3_4
Genetic Epilepsy Modeling With Human Pluripotent Stem Cells
Dang, L. T., & Parent, J. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804066-9.00017-1
Axonal outgrowth and functional recovery after stroke
Ueno, Y., Tanaka, R., Urabe, T., & Hattori, N. (2018) · Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism) · doi:10.16977/cbfm.30.1_65
Developing a neural implant to enable controlled alterations to brain architecture
Weir, N. (2019) · Nottingham Trent University's Institutional Repository (Nottingham Trent Repository)
Grafting purified cortical pericytes into mouse motor cortex
Ganesh, M. G. (2020) · Otago University Research Archive (University of Otago)
The Impact of Aging and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans
Popa‐Wagner, A., Popescu-Drigă, M. V., & Glăvan, D. (2021) · Contemporary clinical neuroscience · doi:10.1007/978-3-030-54564-2_12
Enhancing Stroke Recovery With Cellular Therapies
Satani, N., Parsha, K., & Savitz, S. I. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-69424-7.00062-4
Neurogenesis of Cerebral Cortex Projection Neurons
Hevner, R. F. (2022) · Springer eBooks · doi:10.1007/978-1-4614-6434-1_185-1
Self-citationMartínez-Curiel, R., Hayj, M., Tsupykov, O., Jansson, L., Avaliani, N., Martín, B. C.-S., Monni, E., Skibo, G. G., Lindvall, O., Palma-Tortosa, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.15.585240
Self-citationSharma, D., & Srivastava, S. (2025) · Wiley eBooks · doi:10.1002/9781394313785.ch7
Yamashita, H., Kikuchi, T., Kodaka, Y., Doi, D., Ikeda, M., & Takahashi, J. A. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10981-x · Cited by 3
Molecular mechanisms orchestrating commissural axon guidance
Roig‐Puiggros, S. (2019) · theses.fr (ABES) · doi:10.70675/9709d6aaz37b7z4de2za537zd7f1bf648566
Heterogeneity and clinical potential of boundary cap cells and their derivatives
Gerschenfeld, G. (2019) · theses.fr (ABES) · doi:10.70675/4f41aacezeb93z418cz91d7zfc387d2b3181
Diversity of visual projections in vertebrates
Vigouroux, R. J. (2020) · theses.fr (ABES) · doi:10.70675/4e013149z524az4f80za5c1z99a2ca079cb0
Biomaterial platforms for enhanced stem cell therapy in ischemic stroke
Sun, Z., Zhao, J., Li, J., Ma, X., Wang, Z., Wang, Y., Li, Y., Bai, Y., Wei, D., & Jiang, W. (2026) · Biomaterials · doi:10.1016/j.biomaterials.2026.124427
Chen, K. S., Loi, K. J., McGinley, L. M., Kashlan, O. N., Rigan, D. M., Mason, S. N., Kwentus, J. F., Carter, A., Savelieff, M. G., & Feldman, E. L. (2026) · Current Protocols · doi:10.1002/cpz1.70442
Gómez‐Oliva, R., Helgueta, S., Alonso-Galeron, N., Cambier, A., Ghanavatinejad, F., Masset, G., Collin, L., Nunez‐Abades, P., Hernández‐Galán, R., Castro, C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.25.754353
Human brain cellular xenografts in neuroimmunology and beyond
Fattorelli, N., Martínez‐Muriana, A., Perry, V. H., & Mancuso, R. (2026) · Immunity · doi:10.1016/j.immuni.2026.09.024
Metadata
- Authors
- Tornero, D., Wattananit, S., Grønning Madsen, M., Koch, P., Wood, J., Tatarishvili, J., Mine, Y., Ge, R., Monni, E., Devaraju, K., Hevner, R. F., Brüstle, O., Lindvall, O., & Kokaia, Z.
- Affiliations
- Skåne University Hospital (SE)
- University of Bonn (DE)
- Seattle Children's Research Institute (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-21
- Volume
- 136
- Issue
- 12
- Pages
- 3561-3577
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2045757887
- Cited by
- 241
- References
- 41
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 8 · 2023: 14 · 2022: 10 · 2021: 19 · 2020: 30 · 2019: 27 · 2018: 29 · 2017: 27 · 2016: 17 · 2015: 27 · 2014: 14 · 2013: 1
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Association of Fraternity/Sorority Advisors Foundation
- European Commission (279017)
- Deutsche Forschungsgemeinschaft (SFB TR 3)
- Bundesministerium für Bildung und Forschung (01GN0813)
- Vetenskapsrådet
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- stroke, induced pluripotent stem cells, cortical neurons, neural transplantation, functional recovery, Tbr1, axonal projections, electrophysiological maturation, rat stroke model, tumor formation
- MeSH terms
- Action Potentials, Animals, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Electric Stimulation, Glutaminase, Humans, Neurons, Rats, Nude, Rats, Sprague-Dawley, Neurotransmitter Agents, Patch-Clamp Techniques, Recovery of Function, Infarction, Middle Cerebral Artery, Green Fluorescent Proteins, Rats, Induced Pluripotent Stem Cells
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