Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. 2011

Satoshi Nori, and Yohei Okada, and Akimasa Yasuda, and Osahiko Tsuji, and Yuichiro Takahashi, and Yoshiomi Kobayashi, and Kanehiro Fujiyoshi, and Masato Koike, and Yasuo Uchiyama, and Eiji Ikeda, and Yoshiaki Toyama, and Shinya Yamanaka, and Masaya Nakamura, and Hideyuki Okano
Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan.

Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which do not entail ethical concerns, may become a preferred cell source for regenerative medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI). For this, we used a hiPSC clone (201B7), established by transducing four reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc) into adult human fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the three major neural lineages (neurons, astrocytes, and oligodendrocytes) within the injured spinal cord. They showed both cell-autonomous and noncell-autonomous (trophic) effects, including synapse formation between hiPSC-NS-derived neurons and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal regrowth, and increased amounts of myelin in the injured area. These positive effects resulted in significantly better functional recovery compared with vehicle-treated control animals, and the recovery persisted through the end of the observation period, 112 d post-SCI. No tumor formation was observed in the hiPSC-NS-grafted mice. These findings suggest that hiPSCs give rise to neural stem/progenitor cells that support improved function post-SCI and are a promising cell source for its treatment.

UI MeSH Term Description Entries
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090062 Kruppel-Like Factor 4 A member of zinc finger-containing transcription factors that belongs to the KRUPPEL-LIKE FACTOR family, involved in the regulation of diverse cellular processes such as cell growth, proliferation, differentiation, and APOPTOSIS. EZF Protein,Endothelial Kruppel-Like Zinc Finger Protein,Epithelial Zinc Finger Protein,GKLF Protein,Gut-Enriched Kruppel-Like Factor,Klf4 Protein,Krueppel-Like-Factor 4,4, Krueppel-Like-Factor,4, Kruppel-Like Factor,Endothelial Kruppel Like Zinc Finger Protein,Factor 4, Kruppel-Like,Factor, Gut-Enriched Kruppel-Like,Gut Enriched Kruppel Like Factor,Kruppel Like Factor 4,Protein, EZF,Protein, GKLF,Protein, Klf4
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013119 Spinal Cord Injuries Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.). Myelopathy, Traumatic,Injuries, Spinal Cord,Post-Traumatic Myelopathy,Spinal Cord Contusion,Spinal Cord Laceration,Spinal Cord Transection,Spinal Cord Trauma,Contusion, Spinal Cord,Contusions, Spinal Cord,Cord Contusion, Spinal,Cord Contusions, Spinal,Cord Injuries, Spinal,Cord Injury, Spinal,Cord Laceration, Spinal,Cord Lacerations, Spinal,Cord Transection, Spinal,Cord Transections, Spinal,Cord Trauma, Spinal,Cord Traumas, Spinal,Injury, Spinal Cord,Laceration, Spinal Cord,Lacerations, Spinal Cord,Myelopathies, Post-Traumatic,Myelopathies, Traumatic,Myelopathy, Post-Traumatic,Post Traumatic Myelopathy,Post-Traumatic Myelopathies,Spinal Cord Contusions,Spinal Cord Injury,Spinal Cord Lacerations,Spinal Cord Transections,Spinal Cord Traumas,Transection, Spinal Cord,Transections, Spinal Cord,Trauma, Spinal Cord,Traumas, Spinal Cord,Traumatic Myelopathies,Traumatic Myelopathy

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