TY - JOUR
T1 - Brain from bone
T2 - Efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent
AU - Kohyama, Jun
AU - Abe, Hitoshi
AU - Shimazaki, Takuya
AU - Koizumi, Amane
AU - Nakashima, Kinichi
AU - Gojo, Satoshi
AU - Taga, Tetsuya
AU - Okano, Hideyuki
AU - Hata, Jun Ichi
AU - Umezawa, Akihiro
N1 - Funding Information:
Acknowledgements We are grateful to Dr. Yoshiko Takahashi for xNoggin/MC BOS. We also thank A. Thomson for critically reviewing the manuscript, K. Sakurada, F. Konishi, S. Higashi, Y. Uchida, T. Takizawa, W. Ochiai, M. Yanagisawa, Y. Takahashi, Y. Izawa, M. Fukuma, J. Ozawa, M. Takamatsu, S. Kusakari, Y. Yamada and T. Yamada for advice, and A. Kaneko for technical advice and discussion. This work was supported by a grant from the Ministry of Education, Science and Culture, and by Keio University Special Grant-in-Aid for Innovative Collaborative Research Project.
PY - 2001/10
Y1 - 2001/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035495740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035495740&partnerID=8YFLogxK
U2 - 10.1046/j.1432-0436.2001.680411.x
DO - 10.1046/j.1432-0436.2001.680411.x
M3 - Article
C2 - 11776476
AN - SCOPUS:0035495740
SN - 0301-4681
VL - 68
SP - 235
EP - 244
JO - Differentiation
JF - Differentiation
IS - 4-5
ER -
