Abstract
Radiation therapy is the most widely used and effective treatment for orbital tumors, but it causes dry eye due to lacrimal gland damage. Induced pluripotent stem cell-derived conditioned medium (iPSC-CM) has been shown to rescue different types of tissue damage. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSC-CM) on gamma-irradiation-induced lacrimal gland injury (RILI) in experimental mice. In this study, we found that iPSC-CM ameliorated RILI. iPSC-CM markedly decreased radiotherapy induced inflammatory processes, predominantly through suppressing p38/JNK signaling. Further signaling pathway analyses indicated that iPSC-CM could suppress Akt (Protein Kinase B, PKB) phosphorylation. High levels of midkine (MDK) were also found in iPSC-CM and could be involved in lacrimal gland regeneration by promoting cell migration and proliferation. Thus, our study indicates that inhibiting the p38/JNK pathway or increasing the MDK level might be a therapeutic target for radiation-induced lacrimal gland injury.
Highlights
Radiotherapy-induced lacrimal gland injury (RILGI) is a major clinical concern for patients receiving malignant tumor radiotherapy [1,2,3]
The lacrimal gland of iPS cell-derived conditioned medium (iPSC-CM)-treated RILI and normal animal groups displayed a pattern of hemorrhaging, severe congestion and enlargement due to edema (Figure 1A)
Another study further indicated that iPSC and iPSC-CM both attenuated inflammatory injury through macrophage inflammatory protein-2, urokinase plasminogen activator, angiopoietin-1, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-4, which all contribute to the decrease in inflammation [11]. iPSCs exert immunomodulatory effects, as observed by the prevention of allergic airway inflammation [25]
Summary
Radiotherapy-induced lacrimal gland injury (RILGI) is a major clinical concern for patients receiving malignant tumor radiotherapy [1,2,3]. Radiation damages lacrimal gland cells, resulting in cellular degeneration, necrosis and apoptosis [4]; tear secretion is impaired, and xerophthalmia is induced [1,2,5]. LGE cells are necessary for tear secretion, and their proliferation and migration are crucial for lacrimal gland repair [8,9]. Bone marrow mesenchymal stem cells demonstrate promising improvement of the re-epithelization process and a reduction in T-cell infiltration and proliferation in a rat model of radiation [10]. Studies indicate that mesenchymal stem cells can effectively contribute to lacrimal gland epithelial cell repair after experimentally induced inflammation injury [8,9]. The treatment efficacy of iPS cell-derived conditioned medium (iPSC-CM) in restoring lung epithelial structural damage and suppressing neutrophil infiltration has been demonstrated in ventilator-induced lung injury [11]. The stem cell therapy-based biomolecular mechanisms that improve RILGI inflammation remain unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
