title: Neural progenitors derived from human induced pluripotent stem cells survive and differentiate upon transplantation into a rat model of amyotrophic lateral sclerosis.
abstract: Human induced pluripotent stem cells (iPSCs) offer hope for personalized regenerative cell therapy in amyotrophic lateral sclerosis (ALS). We analyzed the fate of human iPSC-derived neural progenitors transplanted into the spinal cord of wild-type and transgenic rats carrying a human mutated SOD1(G93A) gene. The aim was to follow survival and differentiation of human neural progenitors until day 60 post-transplantation in two different in vivo environments, one being ALS-like. iPSC-derived neural progenitors efficiently engrafted in the adult spinal cord and survived at high numbers. Different neural progenitor, astroglial, and neuronal markers indicated that, over time, the transplanted nestin-positive cells differentiated into cells displaying a neuronal phenotype in both wild-type and transgenic SOD1 rats. Although a transient microglial phenotype was detected at day 15, astroglial staining was negative in engrafted cells from day 1 to day 60. At day 30, differentiation toward a neuronal phenotype was identified, which was further established at day 60 by the expression of the neuronal marker MAP2. A specification process into motoneuron-like structures was evidenced in the ventral horns in both wild-type and SOD1 rats. Our results demonstrate proof-of-principle of survival and differentiation of human iPSC-derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSC-based therapy in ALS.
authors: Université Libre de Bruxelles, Brussels, Belgium.
authors: Iuliana Ristea
authors: IR
authors: Popescu
authors: Charles
authors: C
authors: Nicaise
authors: Song
authors: S
authors: Liu
authors: Grégoire
authors: G
authors: Bisch
authors: Sarah
authors: S
authors: Knippenberg
authors: Valery
authors: V
authors: Daubie
authors: Delphine
authors: D
authors: Bohl
authors: Roland
authors: R
authors: Pochet
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005240:Feasibility Studies; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors
chemical_list: D015415:Biomarkers; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase