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

被引：50

作者：

Yun, Young In ^{[1
]}

Park, Seyeon ^{[2
]}

Lee, Hyun Ju ^{[2
]}

Ko, Jung Hwa ^{[2
]}

Kim, Mee Kum ^{[2
,3
]}

Wee, Won Ryang ^{[2
,3
]}

Reger, Roxanne L. ^{[4
]}

Gregory, Carl A. ^{[4
]}

Choi, Hosoon ^{[4
]}

Fulcher, Samuel F. ^{[5
]}

Prockop, Darwin J. ^{[4
]}

Oh, Joo Youn ^{[2
,3
]}

机构：

[1] Seoul Natl Univ, Coll Med, Seoul, South Korea

[2] Seoul Natl Univ Hosp, Lab Ocular Regenerat Med & Immunol, Seoul, South Korea

[3] Seoul Natl Univ Hosp, Dept Ophthalmol, 101 Daehak Ro, Seoul 110744, South Korea

[4] Scott & White Mem Hosp & Clin, Coll Med, Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Temple, TX USA

[5] Cent Texas Vet Hlth Care Syst, Ophthalmol Sect, Dept Surg, Temple, TX USA

来源：

CYTOTHERAPY | 2017年 / 19卷 / 01期

关键词：

bone marrow; cornea; induced pluripotent stem cell; inflammation; mesenchymal stromal cells; STEM/PROGENITOR CELLS; INFLAMMATORY DAMAGE; PROTEIN TSG-6; TNF-ALPHA; HETEROGENEITY; MSCS; EXPANSION; ONSET;

D O I：

10.1016/j.jcyt.2016.10.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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)-alpha, interleukin (IL)-1 beta 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-alpha 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.

引用

页码：28 / 35

页数：8

共 28 条

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