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Cytotherapy. 2017 Jan;19(1):28-35. doi: 10.1016/j.jcyt.2016.10.007. Epub 2016 Nov 10.

Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury.

Author information

1
College of Medicine, Seoul National University, Seoul, Republic of Korea.
2
Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea.
3
Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea.
4
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, USA.
5
Department of Surgery, Ophthalmology Section, Central Texas Veterans Health Care System, Temple, Texas, USA.
6
Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jooyounoh77@gmail.com.

Abstract

BACKGROUND AIMS:

Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs.

METHODS:

To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation.

RESULTS:

We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity.

CONCLUSIONS:

Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.

KEYWORDS:

bone marrow; cornea; induced pluripotent stem cell; inflammation; mesenchymal stromal cells

PMID:
27840134
DOI:
10.1016/j.jcyt.2016.10.007
[Indexed for MEDLINE]

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