Intranasal administration of human umbilical cord mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke.
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.
Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Qiuchen
Q
Zhao
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jinxia
J
Hu
Department of Rehabilitation Medicine, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jie
J
Xiang
Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Yuming
Y
Gu
Department of Plastic Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Peisheng
P
Jin
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Fang
F
Hua
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Zunsheng
Z
Zhang
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Yonghai
Y
Liu
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Kun
K
Zan
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Zuohui
Z
Zhang
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jie
J
Zu
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Xinxin
X
Yang
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Hongjuan
H
Shi
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jienan
J
Zhu
Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Yun
Y
Xu
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Guiyun
G
Cui
Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: xinchunye@gmail.com.
Xinchun
X
Ye
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000378:metabolism*; D009460:Neurologic Examination; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D017077:Culture Media, Conditioned; D003893:Desmin; C569044:Tjp1 protein, rat; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor
Angiopoietin; Conditioned medium; Human umbilical cord mesenchymal stem cells; Intranasal administration; Vascular remodeling