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

• Published in: Cytotherapy (Oxford, England) Vol. 19; no. 1; pp. 28 - 35
• Main Authors: Yun, Young In, Park, Se Yeon, Lee, Hyun Ju, Ko, Jung Hwa, Kim, Mee Kum, Wee, Won Ryang, Reger, Roxanne L, Gregory, Carl A, Choi, Hosoon, Fulcher, Samuel F, Prockop, Darwin J, Oh, Joo Youn
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.01.2017
• Subjects: Advanced Basic Science; Animals; bone marrow; Bone Marrow Cells - cytology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; cornea; Corneal Injuries - metabolism; Corneal Injuries - therapy; Corneal Opacity - pathology; Corneal Opacity - therapy; Disease Models, Animal; induced pluripotent stem cell; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - transplantation; inflammation; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Keratitis - pathology; Keratitis - therapy; Mesenchymal Stem Cell Transplantation; mesenchymal stromal cells; Mesenchymal Stromal Cells - cytology; Mice, Inbred BALB C; Other; Tumor Necrosis Factor-alpha - metabolism; induced pluripotent stem cell; cornea; inflammation; bone marrow; mesenchymal stromal cells
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2016.10.007

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.