Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells.
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.
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
Kimmo A
KA
Michelsen
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
Sandra
S
Acosta-Verdugo
INSERM U1084, Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group, University of Poitiers, 1 rue Georges Bonnet, BP 633, 86022 Poitiers Cedex, France.
Marianne
M
Benoit-Marand
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
Ira
I
Espuny-Camacho
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
Nicolas
N
Gaspard
INSERM U1084, Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group, University of Poitiers, 1 rue Georges Bonnet, BP 633, 86022 Poitiers Cedex, France.
Bhaskar
B
Saha
INSERM U1084, Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group, University of Poitiers, 1 rue Georges Bonnet, BP 633, 86022 Poitiers Cedex, France. Electronic address: afsaneh.gaillard@univ-poitiers.fr.
Afsaneh
A
Gaillard
Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium; WELBIO, Université Libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium. Electronic address: pierre.vanderhaeghen@ulb.ac.be.
Pierre
P
Vanderhaeghen
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology* / Q000648:ultrastructure; D053595:Embryonic Stem Cells / Q000502:physiology* / Q000637:transplantation* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D039904:Pluripotent Stem Cells / Q000502:physiology / Q000637:transplantation / Q000648:ultrastructure