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

Sung Su An, Hong Lian Jin, Keung Nyun Kim, Hyun Ah Kim, Dong Seok Kim, Joon Cho, Meng Lu Liu, Jin Soo Oh, Do Heum Yoon, Min Hyung Lee, Yoon Ha

Research output: Contribution to journalArticle

18 Citations (Scopus)

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% CO 2 for 24 h. Each group was then cultivated under hypoxic conditions (1% O 2 ) 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.

Original languageEnglish
Pages (from-to)323-331
Number of pages9
JournalChild's Nervous System
Volume26
Issue number3
DOIs
Publication statusPublished - 2010 Jan 1

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Neuroprotective Agents
Mesenchymal Stromal Cells
Vascular Endothelial Growth Factor A
Bone Marrow
Genetic Therapy
Stem Cells
Therapeutics
Cell- and Tissue-Based Therapy
Apoptosis
Neurons
Hypoxia
Annexin A5
Carbon Monoxide
Reverse Transcription
Transfection
Polymerase Chain Reaction
Control Groups
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

An, Sung Su ; Jin, Hong Lian ; Kim, Keung Nyun ; Kim, Hyun Ah ; Kim, Dong Seok ; Cho, Joon ; Liu, Meng Lu ; Oh, Jin Soo ; Yoon, Do Heum ; Lee, Min Hyung ; Ha, Yoon. / Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment. In: Child's Nervous System. 2010 ; Vol. 26, No. 3. pp. 323-331.
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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{\%} CO 2 for 24 h. Each group was then cultivated under hypoxic conditions (1{\%} O 2 ) 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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An, SS, Jin, HL, Kim, KN, Kim, HA, Kim, DS, Cho, J, Liu, ML, Oh, JS, Yoon, DH, Lee, MH & Ha, Y 2010, 'Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment', Child's Nervous System, vol. 26, no. 3, pp. 323-331. https://doi.org/10.1007/s00381-009-1040-2

Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment. / An, Sung Su; Jin, Hong Lian; Kim, Keung Nyun; Kim, Hyun Ah; Kim, Dong Seok; Cho, Joon; Liu, Meng Lu; Oh, Jin Soo; Yoon, Do Heum; Lee, Min Hyung; Ha, Yoon.

In: Child's Nervous System, Vol. 26, No. 3, 01.01.2010, p. 323-331.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment

AU - An, Sung Su

AU - Jin, Hong Lian

AU - Kim, Keung Nyun

AU - Kim, Hyun Ah

AU - Kim, Dong Seok

AU - Cho, Joon

AU - Liu, Meng Lu

AU - Oh, Jin Soo

AU - Yoon, Do Heum

AU - Lee, Min Hyung

AU - Ha, Yoon

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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% CO 2 for 24 h. Each group was then cultivated under hypoxic conditions (1% O 2 ) 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.

AB - 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% CO 2 for 24 h. Each group was then cultivated under hypoxic conditions (1% O 2 ) 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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