Browsing by Subject "VERSUS-HOST-DISEASE"

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  • Willcox, Mark D. P.; Argueso, Pablo; Georgiev, Georgi A.; Holopainen, Juha M.; Laurie, Gordon W.; Millar, Tom J.; Papas, Eric B.; Rolland, Jannick P.; Schmidt, Tannin A.; Stahl, Ulrike; Suarez, Tatiana; Subbaraman, Lakshman N.; Ucakhan, Omur O.; Jones, Lyndon (2017)
    The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership. (C) 2017 Elsevier Inc. All rights reserved.
  • Salmenkari, Hanne; Laitinen, Anita; Forsgård, Richard A.; Holappa, Mervi; Linden, Jere; Pasanen, Lauri; Korhonen, Matti; Korpela, Riitta; Nystedt, Johanna (2019)
    Background: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various preclinical and clinical IBD studies is also challenging due to a large variation in study designs. Methods: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryo-preserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1 beta and tumor necrosis factor (TNF)alpha concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1 beta and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis. Results: Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1 beta protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon. Conclusions: In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.