title: Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation.
abstract: Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. dezawa@anat2.med.kyoto-u.ac.jp
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanno
authors.forename: Mikio
authors.initials: M
authors.lastname: Hoshino
authors.forename: Hirotomi
authors.initials: H
authors.lastname: Cho
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Itokazu
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Tajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Hajime
authors.initials: H
authors.lastname: Sawada
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Toshirou
authors.initials: T
authors.lastname: Mimura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitada
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Chizuka
authors.initials: C
authors.lastname: Ide
mesh_terms: D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017690:Cell Transplantation; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D051880:Receptors, Notch; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014182:Transplantation, Autologous; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020934:Ciliary Neurotrophic Factor; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D051880:Receptors, Notch; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D014446:Tyrosine 3-Monooxygenase