PMID- 31202832 OWN - NLM STAT- MEDLINE DCOM- 20200214 LR - 20200214 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 185 DP - 2019 Aug TI - Traditional two-dimensional mesenchymal stem cells (MSCs) are better than spheroid MSCs on promoting retinal ganglion cells survival and axon regeneration. PG - 107699 LID - S0014-4835(18)30929-1 [pii] LID - 10.1016/j.exer.2019.107699 [doi] AB - The loss of retinal ganglion cells (RGCs) is one of the common pathological features associated with optic nerve diseases leading to blindness. The aims of our study were to compare the neuroprotection of two forms of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on RGCs and axon regeneration after optic nerve crush (ONC) in vivo, and to investigate the molecular mechanism. The effects of intravitreally transplanted hUCB-MSCs cultured in two-dimensional (2D-MSCs) and spheroids (3D-MSCs) were assessed by the survival of RGCs, regenerating axons, and flash visual evoked potentials (fVEP); the level of signal factors secreted by transplanted MSCs in vitreous and the marker protein levels of JAK/STAT3, PI3K/Akt/mTOR and MAPK/ERK pathways were detected using Bead-Based analysis and Western blot, respectively. We found that RGCs began to lose at day 3 after ONC, rapidly decreased at day 7, and flattened at day 14. The neuroprotection of transplanted 2D-MSCs was much stronger than that of 3D-MSCs. The transplanted 2D-MSCs could survive at least 2 weeks without differentiation and keep the characters of MSCs, which secreted multiple tropic factors and accompanied by activation of JAK/STAT3 and MAPK/ERK signaling pathways, top three most abundant factors: stem cell growth factor- beta (SCGF-beta), hepatocyte growth factor (HGF), and monocyte chemoattractant protein-1 (MCP-1). These results indicate that intravitreal injection of 2D-MSCs is a promising therapeutic strategy for retinal pathological diseases characterized by the loss of RGCs and open the door for the application of SCGF-beta, HGF, and MCP-1 in the treatment of optic nerve diseases. CI - Copyright (c) 2019. Published by Elsevier Ltd. FAU - Huang, Wei AU - Huang W AD - Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. FAU - Wang, Cong AU - Wang C AD - Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. FAU - Xie, Lili AU - Xie L AD - Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. FAU - Wang, Xiaoling AU - Wang X AD - Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. FAU - Zhang, Lusi AU - Zhang L AD - Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. FAU - Chen, Changzheng AU - Chen C AD - Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. FAU - Jiang, Bing AU - Jiang B AD - Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, 410011, China. Electronic address: drjiangb@csu.edu.cn. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190613 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (Biomarkers) SB - IM MH - Animals MH - Axons/*physiology MH - Biomarkers/metabolism MH - Blotting, Western MH - Cell Survival/physiology MH - Cells, Cultured MH - Evoked Potentials, Visual/physiology MH - Fetal Blood/cytology MH - Humans MH - Intravitreal Injections MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Nerve Regeneration/*physiology MH - Optic Nerve Injuries/*metabolism MH - Photic Stimulation MH - Retinal Ganglion Cells/*physiology MH - Spheroids, Cellular/cytology OTO - NOTNLM OT - Human umbilical cord blood-derived mesenchymal stem cells OT - Neuroprotection OT - Optic nerve crush OT - Retinal ganglion cells OT - Spheroid OT - Two-dimensional EDAT- 2019/06/17 06:00 MHDA- 2020/02/15 06:00 CRDT- 2019/06/17 06:00 PHST- 2018/12/21 00:00 [received] PHST- 2019/05/09 00:00 [revised] PHST- 2019/06/12 00:00 [accepted] PHST- 2019/06/17 06:00 [pubmed] PHST- 2020/02/15 06:00 [medline] PHST- 2019/06/17 06:00 [entrez] AID - S0014-4835(18)30929-1 [pii] AID - 10.1016/j.exer.2019.107699 [doi] PST - ppublish SO - Exp Eye Res. 2019 Aug;185:107699. doi: 10.1016/j.exer.2019.107699. Epub 2019 Jun 13.