Area-Specific Reestablishment of Damaged Circuits in the Adult Cerebral Cortex by Cortical Neurons Derived from Mouse Embryonic Stem Cells
Open accessAbstract
Pluripotent stem-cell-derived neurons constitute an attractive source for replacement therapies, but their utility remains unclear for cortical diseases. Here, we show that neurons of visual cortex identity, differentiated in vitro from mouse embryonic stem cells (ESCs), can be transplanted successfully following a lesion of the adult mouse visual cortex. Reestablishment of the damaged pathways included long-range and reciprocal axonal projections and synaptic connections with targets of the damaged cortex. Electrophysiological recordings revealed that some grafted neurons were functional and responsive to visual stimuli. No significant integration was observed following grafting of the same neurons in motor cortex, or transplantation of embryonic motor cortex in visual cortex, indicating that successful transplantation required a match in the areal identity of grafted and lesioned neurons. These findings demonstrate that transplantation of mouse ESC-derived neurons of appropriate cortical areal identity can contribute to the reconstruction of an adult damaged cortical circuit.
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Transplanted human neurons develop more slowly than similarly transplanted mouse neurons.
“transplanted human neurons develop more slowly than similarly transplanted mouse neurons”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Michelsen et al., 2015
The ‘Progressive Axonal Outgrowth’ section (page not available) documents the development of transplanted mouse ESC-derived cortical neurons, including increasing axonal growth over the first month. Our copy does not compare their developmental pace with transplanted human neurons, so it does not establish that human neurons develop more slowly. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMouse neurons transplanted in the mouse cortex mature in only a few weeks as the host cortical neurons.
“This is in stark contrast to mouse neurons transplanted in the mouse cortex, which mature in only a few weeks as the host cortical neurons”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Michelsen et al., 2015
In “Progressive Axonal Outgrowth” (page unavailable), the paper reports neuronal differentiation and long-range axonal growth within one month, supporting development over a few weeks. But “Reciprocal Connectivity” (page unavailable) reports no detectable graft-to-host synapses at one month; they were detected at 3–4 months. The source therefore does not establish that the transplanted neurons matured to the level of host cortical neurons in only a few weeks. (LLM, conf=0.85)
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References 66 · Cited by 138
Research works printed but not linked: 4
- Friling, S., Andersson, E., Thompson, L.H., Jo ¨nsson, M.E., Hebsgaard, J.B., Nanou, E., Alekseenko, Z., Marklund, U., Kjellander, S., Volakakis, N., et al. (2009). Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. Proc. Natl. Acad. Sci. USA 106, 7613-7618.
- Gaillard, A., Gaillard, F., and Roger, M. (1998a). Neocortical grafting to newborn and adult rats: developmental, anatomical and functional aspects. Adv. Anat. Embryol. Cell Biol. 148, 1-86. Neuron 85, 982-997, March 4, 2015 ª2015 Elsevier Inc. 995
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- Authors
- Michelsen, K. A., Acosta-Verdugo, S., Benoit-Marand, M., Espuny-Camacho, I., Gaspard, N., Saha, B., Gaillard, A., & Vanderhaeghen, P.
- Affiliations
- Université Libre de Bruxelles (BE)
- Inserm (FR)
- Corresponding author
- Gaillard, Afsaneh
- Vanderhaeghen, Pierre
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 85
- Issue
- 5
- Pages
- 982-997
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1970932379
- Cited by
- 138
- References
- 66
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 11 · 2021: 15 · 2020: 13 · 2019: 20 · 2018: 18 · 2017: 14 · 2016: 14 · 2015: 2
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- HAL (submittedVersion)
- Lirias (submittedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-09-MNPS-0027)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- embryonic stem cell-derived neurons, neural transplantation, visual cortex, axonal projections, synaptic integration, motor cortex, stroke, mouse model
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neurons, Pluripotent Stem Cells, Mice, Embryonic Stem Cells
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