Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin
Abstract
With recent progress in neuroscience and stem-cell research, neural transplantation has emerged as a promising therapy for treating CNS diseases. The success of transplantation has been limited, however, by the restricted ability of neural implants to survive and establish neuronal connections with the host. Little is known about the mechanisms responsible for this failure. Neural implantation triggers reactive gliosis, a process accompanied by upregulation of intermediate filaments in astrocytes and formation of astroglial scar tissue. Here we show that the retinas of adult mice deficient in glial fibrillary acidic protein and vimentin, and consequently lacking intermediate filaments in reactive astrocytes and Müller cells, provide a permissive environment for grafted neurons to migrate and extend neurites. The transplanted cells integrated robustly into the host retina with distinct neuronal identity and appropriate neuronal projections. Our results indicate an essential role for reactive astroglial cells in preventing neural graft integration after transplantation.
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Gfap−/−Vim−/− mice support better integration of neural grafts in the retina and neuronal and astrocyte differentiation of neural stem cells transplanted in the hippocampus.
“They also support better integration of neural grafts in the retina (37) and neuronal and astrocyte differentiation of neural stem cells transplanted in the hippocampus (38).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [37]
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Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
Self-citationBringmann, A., Iandiev, I., Pannicke, T., Wurm, A., Hollborn, M., Wiedemann, P., Osborne, N. N., & Reichenbach, A. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.07.001 · Cited by 761 · see citing works
Glial cells in (patho)physiology
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Self-citationProtective Role of Reactive Astrocytes in Brain Ischemia
Li, L., Lundkvist, A., Andersson, D., Wilhelmsson, U., Nagai, N., Pardo, A. C., Nodin, C., Ståhlberg, A., Aprico, K., Larsson, K., et al. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600546 · Cited by 505 · see citing works
Self-citationWilhelmsson, U., Li, L., Pekna, M., Berthold, C.-H., Blom, S., Eliasson, C., Renner, O., Bushong, E., Ellisman, M., Morgan, T. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0820-04.2004 · Cited by 455 · see citing works
Self-citationAttenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
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Self-citationBrenner, M. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.01.055 · Cited by 222 · see citing works
Reactive glial cells: increased stiffness correlates with increased intermediate filament expression
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Self-citationNakazawa, T., Takeda, M., Lewis, G. P., Cho, K.-S., Jiao, J., Wilhelmsson, U., Fisher, S. K., Pekny, M., Chen, D. F., & Miller, J. W. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-1398 · Cited by 168 · see citing works
Self-citationKamphuis, W., Kooijman, L., Orre, M., Stassen, O., Pekny, M., & Hol, E. M. (2015) · Glia · doi:10.1002/glia.22800 · Cited by 155 · see citing works
Self-citationBioengineering strategies for restoring vision
Cehajic-Kapetanovic, J., Singh, M. S., Zrenner, E., & MacLaren, R. E. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00836-4 · Cited by 79 · see citing works
TNFα activates MAPK and Jak-Stat pathways to promote mouse Müller cell proliferation.
Niu, L., Fang, Y., Yao, X., Zhang, Y., Wu, J., Chen, D. F., & Sun, X. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2020.108353 · Cited by 32 · see citing works
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- Authors
- Kinouchi, R., Takeda, M., Yang, L., Wilhelmsson, U., Lundkvist, A., Pekny, M., & Chen, D. F.
- Affiliations
- Harvard University (US)
- Asahikawa Medical College Hospital (JP)
- University of Gothenburg (SE)
- Corresponding author
- Pekny, Milos
- Chen, Dong Feng
- Venue
- Nature Neuroscience
- Published
- 2003-07-06
- Volume
- 6
- Issue
- 8
- Pages
- 863-868
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2063498603
- Cited by
- 229
- References
- 1
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 8 · 2017: 10 · 2016: 7 · 2015: 16 · 2014: 19 · 2013: 13 · 2012: 19
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (R01EY012983, EY012983)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- retinal transplantation, reactive gliosis, astrocytes, Müller cells, glial fibrillary acidic protein, vimentin, intermediate filaments, glial scar, neurite outgrowth, neuronal migration, graft survival
- MeSH terms
- Animals, Cell Movement, Glial Fibrillary Acidic Protein, Neurons, Retina, Vimentin, Mice, Knockout, Mice
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