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Pigment epithelium-derived factor delays cellular senescence of human mesenchymal stem cells in vitro by reducing oxidative stress

Authors

  • Yukun Cao,

    1. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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    • These authors contributed equally to this work.
  • Ting Yang,

    1. Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 15# Changle West Road, Xi'an 710032, Shaanxi Province, China
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    • These authors contributed equally to this work.
  • Chunhu Gu,

    Corresponding author
    • Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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  • Dinghua Yi

    Corresponding author
    • Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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Corresponding author: e-mail: guchunhutga@hotmail.com, guchunhu@fmmu.edu.cn (Chunhu Gu), yidh@fmmu.edu.cn (Dinghua Yi)

Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that represent a promising approach in the field of regenerative medicine; however, this potential diminishes with senescence. Pigment epithelium-derived factor (PEDF) gives some protection by reducing oxidative stress, which is known to accelerate cellular senescence. Thus we hypothesized that PEDF could delay senescence during MSC expansion by reducing oxidative stress. Proliferation and differentiation potentials, oxidative stress, senescence and p53/p16 expressions have been examined. In MSCs cultured under normoxic conditions treated with PEDF, proliferative lifespan in vitro was significantly increased compared with control group not given PEDF, with ∼10 additional population doublings (PD) occurring before terminal growth arrest. Most of the MSCs cultured under normoxic conditions ceased to proliferate after 20–28 PD, while few senescent cells were found in the hypoxic, PEDF-hypoxic and PEDF-normoxic cultures; this was associated with downregulation of p53 and p16 expression and decreased oxidative stress. PEDF also preserved differentiation potentials of MSCs compared with the control group. Thus PEDF suppression of oxidative stress delays cellular senescence and allows greater expansion of MSCs.

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