Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation

Mari Dezawa, Hiroshi Kanno, Mikio Hoshino, Hirotomi Cho, Naoya Matsumoto, Yutaka Itokazu, Nobuyoshi Tajima, Hitoshi Yamada, Hajime Sawada, Hiroto Ishikawa, Toshirou Mimura, Masaaki Kitada, Yoshihisa Suzuki, Chizuka Ide

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1701-1710
Number of pages10
JournalJournal of Clinical Investigation
Volume113
Issue number12
DOIs
StatePublished - Jun 1 2004

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Autologous Transplantation
Mesenchymal Stromal Cells
Stromal Cells
Glial Cell Line-Derived Neurotrophic Factor
Bone Marrow
Transfection
Dopamine
Ciliary Neurotrophic Factor
Osteocytes
Neural Stem Cells
Apomorphine
Tyrosine 3-Monooxygenase
Colforsin
Chondrocytes
Adipocytes
Neuroglia
Action Potentials
Parkinson Disease
Potassium
Transplantation

ASJC Scopus subject areas

  • Medicine(all)

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Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. / Dezawa, Mari; Kanno, Hiroshi; Hoshino, Mikio; Cho, Hirotomi; Matsumoto, Naoya; Itokazu, Yutaka; Tajima, Nobuyoshi; Yamada, Hitoshi; Sawada, Hajime; Ishikawa, Hiroto; Mimura, Toshirou; Kitada, Masaaki; Suzuki, Yoshihisa; Ide, Chizuka.

In: Journal of Clinical Investigation, Vol. 113, No. 12, 01.06.2004, p. 1701-1710.

Research output: Contribution to journalArticle

Dezawa, M, Kanno, H, Hoshino, M, Cho, H, Matsumoto, N, Itokazu, Y, Tajima, N, Yamada, H, Sawada, H, Ishikawa, H, Mimura, T, Kitada, M, Suzuki, Y & Ide, C 2004, 'Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation', Journal of Clinical Investigation, vol. 113, no. 12, pp. 1701-1710. https://doi.org/10.1172/JCI200420935
Dezawa, Mari ; Kanno, Hiroshi ; Hoshino, Mikio ; Cho, Hirotomi ; Matsumoto, Naoya ; Itokazu, Yutaka ; Tajima, Nobuyoshi ; Yamada, Hitoshi ; Sawada, Hajime ; Ishikawa, Hiroto ; Mimura, Toshirou ; Kitada, Masaaki ; Suzuki, Yoshihisa ; Ide, Chizuka. / Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. In: Journal of Clinical Investigation. 2004 ; Vol. 113, No. 12. pp. 1701-1710.
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