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Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

  • Espuny-Camacho I Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Laboratory of Stem Cell Biology and Pharmacology of Neurodegenerative Diseases, Department of Biosciences, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milano, Italy; INGM Foundation, Via Francesco Sforza 35, 20122 Milano, Italy.
  • Michelsen KA Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium.
  • Linaro D Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Theoretical Neurobiology and Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium.
  • Bilheu A Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium.
  • Acosta-Verdugo S Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium.
  • Herpoel A Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium.
  • Giugliano M Theoretical Neurobiology and Neuroengineering Laboratory, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium; Department of Computer Science, University of Sheffield, S1 4DP Sheffield, UK; Laboratory of Neural Microcircuitry, Brain Mind Institute, EPFL, 1015 Lausanne, Switzerland.
  • Gaillard A INSERM U-1084, Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group, University of Poitiers, 86022 Poitiers, France.
  • Vanderhaeghen P Université Libre de Bruxelles (ULB), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; WELBIO, ULB, Brussels, Belgium. Electronic address: pierre.vanderhaeghen@kuleuven.vib.be.
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  • 2018-05-31
Published in:
  • Cell reports. - 2018
brain repair
brain transplantation
cerebral cortex
neural wiring
pluripotent stem cells
Aging
Animals
Axons
Biomarkers
Cerebral Cortex
Human Embryonic Stem Cells
Humans
Mice, Inbred NOD
Mice, SCID
Neurons
Organ Specificity
Pluripotent Stem Cells
Synapses
Telencephalon
Visual Cortex
English The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation.
Language
  • English
Open access status
gold
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Persistent URL
https://folia.unifr.ch/global/documents/180723
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