PMID- 28844046 OWN - NLM STAT- MEDLINE DCOM- 20171102 LR - 20181202 IS - 1468-2079 (Electronic) IS - 0007-1161 (Linking) VI - 101 IP - 11 DP - 2017 Nov TI - Paracrine effects of mesenchymal stem cells on the activation of keratocytes. PG - 1583-1590 LID - 10.1136/bjophthalmol-2016-310012 [doi] AB - AIMS: The purpose of this study is to investigate the impact of mesenchymal stem cell (MSC)-derived soluble factors on the function of keratocytes, with a particular focus on the processes involved in wound healing, including keratocyte activation, migration and proliferation as well as extracellular matrix (ECM) synthesis. METHODS: Primary cultured rabbit keratocytes were treated with MSC-conditioned medium (MSC-CM). The paracrine factors released by bone marrow MSCs were examined by ELISA. Time-lapse microscope was used to examine wound closure in vitro. Mouse model of corneal injury was made by epithelial scraping after ethanol injury. RESULTS: MSC-CM significantly increased the wound closure rate of corneal stromal cells in vitro. This enhancement of wound closure by MSC-CM was due to the promotion of cell migration. MSC-CM enhanced keratocyte survival following ethanol injury via inhibiting apoptosis. The expression of ECM component genes in keratocytes was upregulated by MSC-CM. In addition, MSC-CM promoted corneal epithelial wound healing following chemical injury. A number of wound healing mediators were detected in MSC-CM, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGFbeta1), interleukin 8 (IL8), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1). CONCLUSION: MSC secretes certain factors that accelerate corneal re-epithelialisation. The paracrine effects of MSC on corneal wound healing including improvements in cell viability, migration and ECM formation. CI - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. FAU - Jiang, Zhixin AU - Jiang Z AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. FAU - Liu, Guangjie AU - Liu G AD - Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Meng, Fanlan AU - Meng F AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. FAU - Wang, Weiyi AU - Wang W AD - Department of Ophthalmology, Tianjin Huanhu Hospital, Tianjin, China. FAU - Hao, Peng AU - Hao P AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. FAU - Xiang, Yang AU - Xiang Y AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. FAU - Wang, Yuchuan AU - Wang Y AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. FAU - Han, RuiFang AU - Han R AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. FAU - Li, Fang AU - Li F AD - Nankai University Eye Hospital, Tianjin, China. FAU - Wang, Liming AU - Wang L AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. FAU - Li, Xuan AU - Li X AD - Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China. AD - Nankai University Eye Hospital, Tianjin, China. AD - Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China. LA - eng PT - Journal Article DEP - 20170826 PL - England TA - Br J Ophthalmol JT - The British journal of ophthalmology JID - 0421041 SB - IM MH - Animals MH - Cell Survival MH - Cell- and Tissue-Based Therapy/*methods MH - Cells, Cultured MH - Corneal Injuries/*metabolism/pathology/therapy MH - Corneal Keratocytes/metabolism/*pathology MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Extracellular Matrix/metabolism MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Rabbits MH - *Wound Healing OTO - NOTNLM OT - cornea OT - stem cells OT - wound healing COIS- Competing interests: None declared. EDAT- 2017/08/28 06:00 MHDA- 2017/11/03 06:00 CRDT- 2017/08/28 06:00 PHST- 2016/12/07 00:00 [received] PHST- 2017/06/20 00:00 [revised] PHST- 2017/07/30 00:00 [accepted] PHST- 2017/08/28 06:00 [pubmed] PHST- 2017/11/03 06:00 [medline] PHST- 2017/08/28 06:00 [entrez] AID - bjophthalmol-2016-310012 [pii] AID - 10.1136/bjophthalmol-2016-310012 [doi] PST - ppublish SO - Br J Ophthalmol. 2017 Nov;101(11):1583-1590. doi: 10.1136/bjophthalmol-2016-310012. Epub 2017 Aug 26.