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

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• 作者：Young In Yun¹ ; Se Yeon Park² ; Hyun Ju Lee² ; Jung Hwa Ko² ; Mee Kum Kim² ; ³ ; Won Ryang Wee² ; ³ ; Roxanne L. Reger⁴ ; Carl A. Gregory⁴ ; Hosoon Choi⁴ ; Samuel F. Fulcher⁵ ; Darwin J. Prockop⁴ ; Joo Youn Oh² ; ³ ; ^{jooyounoh77@gmail.com}
• 关键词：bone marrow ; cornea ; induced pluripotent stem cell ; inflammation ; mesenchymal stromal cells
• 刊名：Cytotherapy
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：19
• 期：1
• 页码：28-35
• 全文大小：1245 K
• 卷排序：19

文摘

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.MethodsTo 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.ResultsWe 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.ConclusionsTogether 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.