Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation
Mari Dezawa, … , Yoshihisa Suzuki, Chizuka Ide
Mari Dezawa, … , Yoshihisa Suzuki, Chizuka Ide
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1701-1710. https://doi.org/10.1172/JCI20935.
View: Text | PDF
Article Neuroscience

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

  • Text
  • PDF
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

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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Transcription factors during induction. (A) RT-PCR of rat MSCs, N-MSCs, ...
Transcription factors during induction. (A) RT-PCR of rat MSCs, N-MSCs, 24 hours and 5 days after trophic factor induction in TF-MSCs, and positive control. (B) Western blot of Notch extracellular domain (NECD) and NICD in rat MSCs, N-MSCs, TF-MSCs (5 days after trophic factor induction), and positive control from brain. β-tubulin (tub) as a loading control. (C and D) Generation of MAP-2ab+ cells (green in D) by JAK/STAT inhibitor WHI-P131 administration and subsequent trophic factor induction in rat MSCs. (E and F) Rat MSCs cotransfected with active form of STAT3 (anti-FLAG; green) and NICD, followed by trophic factor induction. Only a small number of cells were positive for MAP-2ab (red). (G and H) Hes1/5 transfection to rat MSCs. Bars in C–H = 80 ∝m.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts