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- Title
Transduction of human EPO into human bone marrow mesenchymal stromal cells synergistically enhances cell-protective and migratory effects.
- Authors
Mi-Hwa Kim; Goang-Won Cho; Seong-Ho Koh; Yong-Min Huh; Seung Hyun Kim
- 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.
- Subjects
BONE marrow; CELLS; ERYTHROPOIETIN; NEURODEGENERATION; CELLULAR therapy
- Publication
Molecular Biology, 2010, Vol 44, Issue 4, p577
- ISSN
0026-8933
- Publication type
Article
- DOI
10.1134/S0026893310040126