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Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment

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Abstract

Purposes

To avoid unwanted adverse effects of higher doses of single treatment of stem cells and gene therapy and increase the therapeutic efficacies, we hypothesized the combined therapy with stem cells and gene therapy. This study assessed the neuroprotective effects of combined gene therapy and stem cell treatment under ischemic hypoxia conditions using hypoxia-inducible vascular endothelial growth factor (VEGF) and bone marrow-derived mesenchymal stem cells (BMSC).

Methods

Experimental groups included the control which was N2A cells transfected with empty vectors, the transfection only group which was N2A cells treated with pEpo-SV-VEGF alone, the BMSC only group which was N2A cells transfected with empty vectors and cocultured with BMSCs, and the combined treatment group which was N2A cells treated with pEpo-SV-VEGF and cocultured with BMSCs. Each group was transfected for 4 h and cultured at 37°C and 5% CO2 for 24 h. Each group was then cultivated under hypoxic conditions (1% O2) for 12 h. Neuroprotective effects were assessed by reverse transcription polymerase chain reaction, annexin V, and cytotoxicity assay.

Results

Neurons exposed to hypoxic conditions exhibited neuronal apoptosis. Compared to single treatments, the combined hypoxia-inducible VEGF and BMSC treatment demonstrated a significant increase in VEGF expression and decreased neuronal apoptosis.

Conclusions

These results suggest that combined pEpo-SV-VEGF and BMSC treatment is effective in protecting neurons against hypoxic ischemic injury.

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Acknowledgments

This study was supported by grants (SC-4180) from Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology.

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Authors and Affiliations

  1. Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Seoul, 120-752, South Korea

    Sung Su An, Hong Lian Jin, Keung Nyun Kim, Dong Seok Kim, Meng-Lu Liu, Jin Soo Oh, Do Heum Yoon & Yoon Ha

  2. Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, 120-750, South Korea

    Sung Su An, Meng-Lu Liu, Jin Soo Oh & Do Heum Yoon

  3. Department of Bioengineering, College of Engineering, Hanyang University, Seoul, South Korea

    Hyun Ah Kim & Min Hyung Lee

  4. Department of Neurosurgery, Konkuk University, Seoul, South Korea

    Joon Cho

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  1. Sung Su An
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  2. Hong Lian Jin
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Correspondence to Yoon Ha.

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An, S.S., Jin, H.L., Kim, K.N. et al. Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment. Childs Nerv Syst 26, 323–331 (2010). https://doi.org/10.1007/s00381-009-1040-2

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  • DOI: https://doi.org/10.1007/s00381-009-1040-2

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