PMID- 26279113 OWN - NLM STAT- MEDLINE DCOM- 20160810 LR - 20181202 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1624 DP - 2015 Oct 22 TI - Intranasal administration of human umbilical cord mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke. PG - 489-496 LID - S0006-8993(15)00607-1 [pii] LID - 10.1016/j.brainres.2015.08.003 [doi] AB - Stem cell-based treatments have been reported to be a potential strategy for stroke. However, tumorigenic potential and low survival rates of transplanted cells could attenuate the efficacy of the stem cell-based treatments. The application of stem cell-condition medium (CM) may be a practicable approach to conquer these limitations. In this study, we investigated whether intranasal administration of human umbilical cord mesenchymal stem cells (hUCMSCs)-CM has the therapeutic effects in rats after stroke. Adult male rats were subjected to middle cerebral artery occlusion (MCAo) and were treated by intranasal routine with or without hUCMSCs-CM (1 ml/kg/d), starting 24h after MCAo and daily for 14 days. Neurological functional tests, blood brain barrier (BBB) leakage, were measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, and Western blot, respectively. hUCMSCs-CM treatment of stroke by intranasal routine starting 24h after MCAo in rats significantly enhances BBB functional integrity and promotes functional outcome but does not decrease lesion volume compared to rats in DMEM/F12 medium control group and saline control group. Treatment of ischemic rats with hUCMSCs-CM by intranasal routine also significantly decreases the levels of Ang2 and increases the levels of both Ang1 and Tie2 in the ischemic brain. To take together, increased expression of Ang1 and Tie2 and decreased expression of Ang2, induced by hUCMSCs-CM treatment, contribute to vascular remodeling in the ischemic brain which plays an important role in functional outcome after stroke. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Zhao, Qiuchen AU - Zhao Q AD - Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Hu, Jinxia AU - Hu J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Xiang, Jie AU - Xiang J AD - Department of Rehabilitation Medicine, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Gu, Yuming AU - Gu Y AD - Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Jin, Peisheng AU - Jin P AD - Department of Plastic Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Hua, Fang AU - Hua F AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zhang, Zunsheng AU - Zhang Z AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Liu, Yonghai AU - Liu Y AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zan, Kun AU - Zan K AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zhang, Zuohui AU - Zhang Z AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zu, Jie AU - Zu J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Yang, Xinxin AU - Yang X AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Shi, Hongjuan AU - Shi H AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Zhu, Jienan AU - Zhu J AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Xu, Yun AU - Xu Y AD - Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. FAU - Cui, Guiyun AU - Cui G AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. FAU - Ye, Xinchun AU - Ye X AD - Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: xinchunye@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150813 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Culture Media, Conditioned) RN - 0 (Desmin) RN - 0 (Tjp1 protein, rat) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Zonula Occludens-1 Protein) RN - 0 (von Willebrand Factor) SB - IM MH - Administration, Intranasal MH - Analysis of Variance MH - Animals MH - Cells, Cultured MH - Culture Media, Conditioned/*pharmacology MH - Desmin/metabolism MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Fetal Blood/*cytology MH - Humans MH - Infarction, Middle Cerebral Artery/*drug therapy/pathology MH - Male MH - Mesenchymal Stem Cells/chemistry/*metabolism MH - Neurologic Examination MH - Rats MH - Vascular Endothelial Growth Factor A/metabolism MH - Vascular Remodeling/*drug effects MH - Zonula Occludens-1 Protein/metabolism MH - von Willebrand Factor/metabolism OTO - NOTNLM OT - Angiopoietin OT - Conditioned medium OT - Human umbilical cord mesenchymal stem cells OT - Intranasal administration OT - Vascular remodeling EDAT- 2015/08/19 06:00 MHDA- 2016/08/11 06:00 CRDT- 2015/08/18 06:00 PHST- 2015/05/19 00:00 [received] PHST- 2015/08/04 00:00 [revised] PHST- 2015/08/05 00:00 [accepted] PHST- 2015/08/18 06:00 [entrez] PHST- 2015/08/19 06:00 [pubmed] PHST- 2016/08/11 06:00 [medline] AID - S0006-8993(15)00607-1 [pii] AID - 10.1016/j.brainres.2015.08.003 [doi] PST - ppublish SO - Brain Res. 2015 Oct 22;1624:489-496. doi: 10.1016/j.brainres.2015.08.003. Epub 2015 Aug 13.