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Dipeptidyl peptidase‐4 (DPP4) induce Cellular Senescence in Human Umbilical Cord Blood‐Derived Mesenchymal Stem Cells
Author(s) -
Kim Miyeon,
Bae Yun Kyung,
Kwon Jihye,
Jeon Hong Bae,
Jin Hye Jin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb40
Subject(s) - mesenchymal stem cell , senescence , stem cell , cell sorting , microbiology and biotechnology , biology , immunology , flow cytometry , cancer research
Recently, the number of clinical trials in which mesenchymal stem cells (MSCs)‐based therapy is employed to treat various diseases has increased. A fundamental requirement for these MSCs‐based therapies is the expansion of MSCs during long‐term growth in culture, which is required to obtain a sufficient number of functional cells. However, long‐term growth inevitably arguments cellular senescence, which potentially causes poor clinical outcomes by inducing growth arrest and the loss of stem cell properties in MSCs. Thus, the identification of suitable markers for evaluating the status of MSCs senescence during long‐term culture is crucial. Here, we investigated the surface markers of human umbilical cord blood‐derived MSCs (hUCB‐MSCs) associated with cellular senescence using fluorescence‐activated cell sorting analysis and 242 cell surface‐marker antibodies. Among these surface proteins, we selected dipeptidyl peptidase‐4 (DPP4) which further validated for their expression by flow cytometer analysis. It has been shown that expression of DPP4 was the markedly increased in the aging hUCB‐MSCs. Through sorting analysis and small interfering RNA treatment, the DPP4 positive hUCB‐MSCs had the low rate of cell growth and differentiation potentials, and significantly higher expression of p38, p53, pRb, and β galactosidase‐positive staining, well known markers of senescence. In addition, suppression of DPP4 in hUCB‐MSCs resulted in up‐regulation of stemness genes, including Oct4, Nanog. Interestingly, DPP4 negative hUCB‐MSCs induced to a greater improvement in therapeutic effect by not only promoting the engraftment potential of infused stem cell, but also reducing lung damage in an emphysema mouse model. Taken together, our results demonstrate that DPP4 is a new marker for predicting senescence in hUCB‐MSCs, and it could be valuable in quality‐control assessments and for improving the therapeutic potential of hUCB‐MSCs‐based therapy.