The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Cited by
Sorted by citations
Steinbeck, J. A., Choi, S. J., Mrejeru, A., Ganat, Y. M., Deisseroth, K. A., Sulzer, D., Mosharov, E. V., & Studer, L. (2015) · Nature Biotechnology · doi:10.1038/nbt.3124 · Cited by 304
Kirkeby, A., Nolbrant, S., Tiklová, K., Heuer, A., Kee, N., Cardoso, T., Ottosson, D. R., Lelos, M. J., Rifes, P., Dunnett, S. B., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.09.004 · Cited by 267
Restoring brain function after stroke — bridging the gap between animals and humans
Ward, N. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.34 · Cited by 247
Neuroprotection for ischaemic stroke: Current status and challenges
Moretti, A., Ferrari, F., & Villa, R. F. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.09.003 · Cited by 242
An epigenetic barrier sets the timing of human neuronal maturation
Ciceri, G., Baggiolini, A., Cho, H. S., Kshirsagar, M., Benito-Kwiecinski, S., Walsh, R. M., Aromolaran, K. A., Gonzalez-Hernandez, A. J., Munguba, H., Koo, S. Y., et al. (2024) · Nature · doi:10.1038/s41586-023-06984-8 · Cited by 240
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
