• Open Access

PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing

Authors

  • Tsung-Chuan Ho,

    1. Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan, Republic of China
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  • Show-Li Chen,

    1. Department of Microbiology, School of Medicine National Taiwan University, Taipei, Taiwan, Republic of China
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  • Ju-Yun Wu,

    1. Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan, Republic of China
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  • Mei-Ying Ho,

    1. Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan, Republic of China
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  • Lee-Jen Chen,

    1. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
    2. Mackay Medicine, Nursing and Management College, Taiwan, Republic of China
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  • Jui-Wen Hsieh,

    1. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
    2. Mackay Medicine, Nursing and Management College, Taiwan, Republic of China
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  • Huey-Chuan Cheng,

    1. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
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  • Yeou-Ping Tsao

    Corresponding author
    1. Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan, Republic of China
    2. Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
    • Mackay Memorial Hospital, Number 92, Sec. 2, Chung Shan North Road, Taipei, Taiwan, Republic of China. E-mail: yptsao@yahoo.com Telephone: 886-2-28094661, ext. 3076; Fax: 886-2-28085952

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  • Author contributions: T.-C.H.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; S.-L.C.: conception and design, data analysis; J.-Y.W.: provision of study material, collection and assembly of data; M.-Y.H.: conception and design, manuscript writing; L.-J.C.: provision of study material, conception and design, data analysis; J.-W.H.: conception and design, data analysis; H.-C.C.: data analysis and interpretation; Y.-P.T.: conception and design, data analysis, interpretation, manuscript writing; and final approval of manuscript.

Abstract

Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78–121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound. STEM Cells 2013;31:1775–1784

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