Brain from bone: Efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent

Jun Kohyama, Hitoshi Abe, Takuya Shimazaki, Amane Koizumi, Kinichi Nakashima, Satoshi Gojo, Tetsuya Taga, Hideyuki Okano, Jun Ichi Hata, Akihiro Umezawa

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270 Citations (Scopus)

Abstract

Bone marrow stromal cells are able to differentiate into adipogenic, chondrogenic, myogenic, osteogenic, and cardiomyogenic lineages, all of which are limited to a mesoderm-derived origin. In this study, we showed that neurons, which are of an ectoderm-origin, could be generated from marrow-derived stromal cells by specific inducers, fibronectin/ornithine coating, and neurosphere formation. The neurons generated from marrow stroma formed neurites, expressed neuron-specific markers and genes, and started to respond to depolarizing stimuli as functional mature neurons. Among stromal cells, isolated mature osteoblasts which had strong in vivo osteogenic activity could be efficiently converted into functional neurons. This transdifferentiation or meta-differentiation was enhanced by Noggin, an inhibitor of bone morphogenetic proteins, in comparison with 5-azacytidine, a demethylating agent capable of altering the gene expression pattern. Marrow stroma is therefore a potential source of cells for neural cell transplantation.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalDifferentiation
Volume68
Issue number4-5
DOIs
Publication statusPublished - Oct 2001
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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