The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)--a preliminary study using microarray analysis.
Bone marrow stromal cells (BMSC) have been anticipated as a donor for cell type for transplantation therapy in various neurological disorders. However, their neurogenic capacity still remains undetermined. In this study, we aimed to clarify whether in vitro chemical treatment promotes their neuronal differentiation on the level of gene expression. Mice BMSC were cultured with medium supplemented with DMSO, retinoic acid, and basic fibroblast growth factor, and their morphology and expression of neuronal markers were evaluated. Subsequently, using microarray and RT-PCR techniques, the treatment-induced changes in the gene expression profile were analyzed. After exposure to the medium, the BMSC simulated a neuron-like appearance and increased their immunoreactivity for nestin and Tuj-1. Microarray analysis revealed that the BMSC per se express the multilineage cellular genes, including those associated with the neuron. Chemical treatment significantly decreased the expression of genes related to mesenchymal cells and increased the expression of 5 neuron-associated genes. Microarray and RT-PCR analyses also demonstrated that the BMSC express the genes for several growth factors including NGF-beta and BDNF, indicating their therapeutic role in protecting the injured central nervous system. The present results suggest that at least a certain subpopulation of the BMSC have the potential to alter their gene expression profile in response to the surrounding environment and may possibly protect the host tissue by secreting neuroprotective factors.
Yamaguchi
Satoshi
S
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060-8638, Japan.
Kuroda
Satoshi
S
Kobayashi
Hiroyuki
H
Shichinohe
Hideo
H
Yano
Shunsuke
S
Hida
Kazutoshi
K
Shinpo
Kazuyoshi
K
Kikuchi
Seiji
S
Iwasaki
Yoshinobu
Y
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008813:Mice, Inbred ICR; D046228:Microarray Analysis / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger