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Published Online: 1 July 2017

Uremic Toxins Affect the Imbalance of Redox State and Overexpression of Prolyl Hydroxylase 2 in Human Adipose Tissue-Derived Mesenchymal Stem Cells Involved in Wound Healing

Publication: Stem Cells and Development
Volume 26, Issue Number 13


Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions. Consistent with the uremic-treated AT-MSCs, there was a definite imbalance of redox state and high expression of ROS in CKD-AT-MSCs isolated from early-stage CKD patients. In addition, a transplantation study clearly revealed that nAT-MSCs promoted the recruitment of inflammatory cells and recovery from ischemia in the mouse flap model, whereas CKD-AT-MSCs had defective functions and the wound healing process was delayed. Of note, the expression of prolyl hydroxylase domain 2 (PHD2) is selectively increased in CKD-AT-MSCs and its inhibition can restore the expression of HIF-1α and the wound healing function of CKD-AT-MSCs. These results indicate that more studies about the functions of MSCs from CKD patients are required before they can be applied in the clinical setting.

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Published In

cover image Stem Cells and Development
Stem Cells and Development
Volume 26Issue Number 13July 1, 2017
Pages: 948 - 963
PubMed: 28537846


Published in print: July 1, 2017
Published online: 1 July 2017
Published ahead of print: 24 May 2017
Accepted: 14 April 2017
Received: 16 November 2016


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Vuong Cat Khanh
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan.
Kinuko Ohneda
Takasaki University of Health and Welfare Laboratory of Molecular Pathophysiology, Takasaki, Japan.
Toshiki Kato
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan.
Toshiharu Yamashita
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan.
Fujio Sato
Department of Cardiovascular Surgery, University of Tsukuba, Tsukuba, Japan.
Kana Tachi
Department of Breast-Thyroid-Endocrine Surgery, University of Tsukuba, Tsukuba, Japan.
Osamu Ohneda
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba, Japan.


Address correspondence to:Prof. Osamu OhnedaGraduate School of Comprehensive Human ScienceLaboratory of Regenerative Medicine and Stem Cell BiologyUniversity of Tsukuba1-1-1 TennoudaiTsukuba 305-8575Japan
E-mail: [email protected]

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No competing financial interests exist.

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