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Enhanced human mesenchymal stem cell survival under oxidative stress by overexpression of secreted frizzled-related protein 2 gene

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Abstract

Human mesenchymal stem cells (hMSCs) have been used to improve engraftment and to treat graft versus host disease following allogeneic hematopoietic stem cell transplantation. However, oxidative stress presented in the microenvironment can damage the transplanted hMSCs and therefore reduce their survival in target organs. We investigated how to enhance the survival of hMSCs under oxidative stress by overexpressing secreted frizzled-related protein 2 (sFRP2) gene in bone marrow-derived hMSCs and umbilical cord-derived hMSCs. The survival and characteristics of those sFRP2-overexpressing hMSCs (sFRP2-BM-hMSCs and sFRP2-UC-hMSCs) were studied compared with non-transduced hMSCs. We found that the percentages of viable cells in culture of sFRP2-BM-hMSCs and sFRP2-UC-hMSCs in the absence or presence of 0.75 mM H2O2 were significantly higher than those of their non-transduced counterparts. The overexpression of sFRP2 gene did not affect the characteristics of hMSCs regarding their morphology, surface marker expression, and differentiation potential. Our study suggests that overexpression of sFRP2 gene in hMSCs might improve the therapeutic effectiveness of hMSC transplantation.

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Abbreviations

AM:

Amnion

BM:

Bone marrow

CO2 :

Carbon dioxide

DMEM:

Dulbecco’s modified Eagle’s medium

H2O2 :

Hydrogen peroxide

hMSCs:

Human mesenchymal stem cells

PBS:

Phosphate-buffered saline

PL:

Placenta

sFRP2:

Secreted frizzled-related protein 2

sFRP2-BM-hMSCs:

Human bone marrow-derived mesenchymal stem cells which are stably transduced with sFRP2 overexpressing plasmid

sFRP2-UC-hMSCs:

Human umbilical cord-derived mesenchymal stem cells which are stably transduced with sFRP2 overexpressing plasmid

UC:

Umbilical cord

WJ:

Wharton’s jelly

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Acknowledgments

This research project was funded by grants from Thailand Research Fund (grant no. RTA 488-0007), the Commission on Higher Education (grant no. CHE-RES-RG-49), Siriraj Graduate Scholarship, and Siriraj Graduate Thesis Scholarship. S. Issaragrisil is a Senior Research Scholar of Thailand Research Fund. There were no commercial organizations or funding bodies associated with data collection and analysis or with this study manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors’ contributions

KP carried out the experiments and helped in drafting the manuscript. PK performed data analysis, participated in the study design, supervised the study, and wrote the manuscript. YU carried out the experiments and performed data analysis. MW participated in data analysis and assisted in drafting the manuscript. NC participated in data analysis and assisted in drafting the manuscript. SI conceived and supervised the study and finalized the manuscript. All of the authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Kanjana Pomduk

  2. Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Kanjana Pomduk, Pakpoom Kheolamai, Yaowalak U-Pratya, Methichit Wattanapanitch, Nuttha Klincumhom & Surapol Issaragrisil

  3. Division of Cell Biology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand

    Pakpoom Kheolamai

  4. Center of Excellence in Stem Cell Research, Faculty of Medicine, Thammasat University, Pathumthani, Thailand

    Pakpoom Kheolamai

  5. Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand

    Yaowalak U-Pratya & Surapol Issaragrisil

Authors
  1. Kanjana Pomduk
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  2. Pakpoom Kheolamai
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Corresponding author

Correspondence to Surapol Issaragrisil.

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Additional file 1

Survival of BM-hMSCs, UC-hMSCs, WJ-hMSCs, PL-hMSCs, and AM-hMSCs under oxidative stress condition generated by the addition of 1 mM H2O2 as determined by flow cytometry using FITC Annexin V Apoptosis Detection Kit I (GIF 40 kb)

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Pomduk, K., Kheolamai, P., U-Pratya, Y. et al. Enhanced human mesenchymal stem cell survival under oxidative stress by overexpression of secreted frizzled-related protein 2 gene. Ann Hematol 94, 319–327 (2015). https://doi.org/10.1007/s00277-014-2210-1

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  • DOI: https://doi.org/10.1007/s00277-014-2210-1

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