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Neurotrophic Actions of Bone Marrow Stromal Cells on Primary Culture of Dorsal Root Ganglion Tissues and Neurons

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Abstract

Application of adult bone marrow stromal cells (BMSCs) provides therapeutic benefits to the treatment of neurological insults. The aim of this study was to explore the potential of nonhematopoietic BMSCs to produce soluble factors and stimulate signaling pathways in neurons that mediate trophic effects. A combination of enzyme-linked immunosorbent assay and two-dimensional gel electrophoresis coupled with mass spectrometry showed that the BMSCs released into the culture medium an array of soluble factors such as nerve growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, and ciliary neurotrophic factor, which have been shown to exhibit potent neurotrophic effects on neural cells. Immunochemistry, cell viability assay, and quantitative real-time RT-PCR collectively showed that neurite outgrowth and neurogenesis in cultured rat dorsal root ganglion (DRG) explants and neurons were enhanced after they were cocultured with rat BMSCs. Western blot analysis revealed that BMSC-conditioned medium activated phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphoinositide 3-kinase/serine/threonine kinase (PI3K/Akt) in primary culture of rat DRG neurons, which suggested that BMSCs trigger endogenous survival signaling pathways in neurons through their secreted soluble factors. Our data help to elucidate the mechanisms by which BMSCs function as a cell therapy agent in peripheral nerve regeneration.

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Acknowledgment

The financial supports of the Hi-Tech Research and Development Program of China (863 Program, grant number 2006AA02A128) and the Nature Science Foundation of China (grant number 30670667) are gratefully acknowledged. We thank Professor Jie Liu for assistance in manuscript preparation.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, People’s Republic of China

    Yun Gu, Jie Wang, Fei Ding, Nan Hu, Yaxian Wang & Xiaosong Gu

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  1. Yun Gu
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  2. Jie Wang
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  3. Fei Ding
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  4. Nan Hu
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  5. Yaxian Wang
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  6. Xiaosong Gu
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Correspondence to Xiaosong Gu.

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Gu, Y., Wang, J., Ding, F. et al. Neurotrophic Actions of Bone Marrow Stromal Cells on Primary Culture of Dorsal Root Ganglion Tissues and Neurons. J Mol Neurosci 40, 332–341 (2010). https://doi.org/10.1007/s12031-009-9304-6

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  • DOI: https://doi.org/10.1007/s12031-009-9304-6

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