title: Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice.
abstract: Spinal muscular atrophy, characterized by selective loss of lower motor neurons, is an incurable genetic neurological disease leading to infant mortality. We previously showed that primary neural stem cells derived from spinal cord can ameliorate the spinal muscular atrophy phenotype in mice, but this primary source has limited translational value. Here, we illustrate that pluripotent stem cells from embryonic stem cells show the same potential therapeutic effects as those derived from spinal cord and offer great promise as an unlimited source of neural stem cells for transplantation. We found that embryonic stem cell-derived neural stem cells can differentiate into motor neurons in vitro and in vivo. In addition, following their intrathecal transplantation into spinal muscular atrophy mice, the neural stem cells, like those derived from spinal cord, survived and migrated to appropriate areas, ameliorated behavioural endpoints and lifespan, and exhibited neuroprotective capability. Neural stem cells obtained using a drug-selectable embryonic stem cell line yielded the greatest improvements. As with cells originating from primary tissue, the embryonic stem cell-derived neural stem cells integrated appropriately into the parenchyma, expressing neuron- and motor neuron-specific markers. Our results suggest translational potential for the use of pluripotent cells in neural stem cell-mediated therapies and highlight potential safety improvements and benefits of drug selection for neuroepithelial cells.
authors.affiliation: Department of Neurological Sciences, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Martina
authors.initials: M
authors.lastname: Nardini
authors.forename: Chiara
authors.initials: C
authors.lastname: Donadoni
authors.forename: Sabrina
authors.initials: S
authors.lastname: Salani
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.forename: Marianna
authors.initials: M
authors.lastname: Falcone
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.forename: Federica
authors.initials: F
authors.lastname: Locatelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Mezzina
authors.forename: Francesca
authors.initials: F
authors.lastname: Gianni
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D010641:Phenotype; D033581:Stem Cell Transplantation