title: Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord.
abstract: Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into free-floating spheres that were easy to maintain and were expandable (EZ spheres) (Ebert et al. [2013] Stem Cell Res 10:417-427). These EZ spheres could be differentiated towards NPC spheres with a spinal cord phenotype using a combination of all-trans retinoic acid (RA) and epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) mitogens. Suspension cultures of NPCs derived from human iPSCs or fetal tissue have similar characteristics, although they were not similar when grown as adherent cells. In addition, iPSC-derived NPCs (iNPCs) survived grafting into the spinal cord of athymic nude rats with no signs of overgrowth and with a very similar profile to human fetal-derived NPCs (fNPCs). These results suggest that human iNPCs behave like fNPCs and could thus be a valuable alternative for cellular regenerative therapies of neurological diseases.
authors.affiliation: Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Sareen
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gowing
authors.forename: Anais
authors.initials: A
authors.lastname: Sahabian
authors.forename: Kevin
authors.initials: K
authors.lastname: Staggenborg
authors.forename: Renée
authors.initials: R
authors.lastname: Paradis
authors.forename: Pablo
authors.initials: P
authors.lastname: Avalos
authors.forename: Jessica
authors.initials: J
authors.lastname: Latter
authors.forename: Loren
authors.initials: L
authors.lastname: Ornelas
authors.forename: Leslie
authors.initials: L
authors.lastname: Garcia
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D013116:Spinal Cord / Q000166:cytology* / Q000601:surgery; D059467:Transcriptome / Q000502:physiology
chemical_list: D051401:Aquaporin 4; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins
keywords: Human iPS cells; neural progenitor cells; astrocytes; cell transplantation; regenerative therapy; ALS