Transduction of human EPO into human bone marrow mesenchymal stromal cells synergistically enhances cell-protective and migratory effects

Mi Hwa Kim, Goang Won Cho, Seong Ho Koh, Yong Min Huh, Seung Hyun Kim

Research output: Contribution to journalArticle

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Abstract

Human bone marrow mesenchymal stromal cells (hBM-MSCs) are a promising tools for cell therapy. However, the poor viability of the transplanted cells is a major limiting factor. Human erythropoietin (hEPO) has been extensively studied in non-hematopoietic tissues for its neurotrophic, anti-oxidant, antiapoptotic, and anti-inflammatory effects. In this study, we evaluate whether transduction of the hEPO gene into MSCs provides protection and affects their migration. hBM-MSCs transduced with the hEPO gene (EPO-MSCs) stably secreted high levels of hEPO (10 IU/ml) with no alteration of their mesenchymal phenotype. MSCs were also treated with 10 IU rhEPO, an amount similar to what was secreted by EPO-MSCs, to generate 10U-MSCs. Protection against H2O2-induced oxidative stress and staurosporine-induced apoptosis was registered for both EPO-MSCs and 10U-MSCs, but the protective effects were higher for the EPO-MSCs than for the 10U-MSCs. EPO-MSCs had significantly higher migration rates compared to MSCs and 10U-MSCs. We confirmed that the intracellular signaling of ERK1/2 was higher in the EPO-MSCs than 10U-MSCs. This data demonstrates that the endogenous expression of EPO may efficiently initiate the ERK1/2 signaling pathway, resulting in synergistic effects on the production of neurotrophic factors. Thus, EPO-MSCs are a good candidate for cell therapy in ischemic and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalMolecular Biology
Volume44
Issue number4
DOIs
Publication statusPublished - 2010 Aug 13

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Mesenchymal Stromal Cells
Erythropoietin
Cell- and Tissue-Based Therapy
Staurosporine
MAP Kinase Signaling System
Nerve Growth Factors
Oxidants
Neurodegenerative Diseases
Genes
Cell Survival
Oxidative Stress
Anti-Inflammatory Agents
Apoptosis
Phenotype

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology

Cite this

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abstract = "Human bone marrow mesenchymal stromal cells (hBM-MSCs) are a promising tools for cell therapy. However, the poor viability of the transplanted cells is a major limiting factor. Human erythropoietin (hEPO) has been extensively studied in non-hematopoietic tissues for its neurotrophic, anti-oxidant, antiapoptotic, and anti-inflammatory effects. In this study, we evaluate whether transduction of the hEPO gene into MSCs provides protection and affects their migration. hBM-MSCs transduced with the hEPO gene (EPO-MSCs) stably secreted high levels of hEPO (10 IU/ml) with no alteration of their mesenchymal phenotype. MSCs were also treated with 10 IU rhEPO, an amount similar to what was secreted by EPO-MSCs, to generate 10U-MSCs. Protection against H2O2-induced oxidative stress and staurosporine-induced apoptosis was registered for both EPO-MSCs and 10U-MSCs, but the protective effects were higher for the EPO-MSCs than for the 10U-MSCs. EPO-MSCs had significantly higher migration rates compared to MSCs and 10U-MSCs. We confirmed that the intracellular signaling of ERK1/2 was higher in the EPO-MSCs than 10U-MSCs. This data demonstrates that the endogenous expression of EPO may efficiently initiate the ERK1/2 signaling pathway, resulting in synergistic effects on the production of neurotrophic factors. Thus, EPO-MSCs are a good candidate for cell therapy in ischemic and neurodegenerative diseases.",
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Transduction of human EPO into human bone marrow mesenchymal stromal cells synergistically enhances cell-protective and migratory effects. / Kim, Mi Hwa; Cho, Goang Won; Koh, Seong Ho; Huh, Yong Min; Kim, Seung Hyun.

In: Molecular Biology, Vol. 44, No. 4, 13.08.2010, p. 577-584.

Research output: Contribution to journalArticle

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