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Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

Authors
 Sung-Rae Cho  ;  Hwal Suh  ;  Ji Hea Yu  ;  Hyongbum (Henry) Kim  ;  Jung Hwa Seo  ;  Cheong Hoon Seo 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.17(9) : 1550, 2016 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2016
MeSH
Animals ; Astrocytes/cytology ; Astrocytes/metabolism ; Astrocytes/physiology* ; Blood Vessels/physiopathology* ; Blotting, Western ; Brain Injuries/etiology ; Brain Injuries/physiopathology ; Brain Injuries/therapy* ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Hypoxia-Ischemia, Brain/complications ; Hypoxia-Ischemia, Brain/physiopathology ; Intercellular Signaling Peptides and Proteins/metabolism ; Male ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/physiology* ; Mice, Inbred ICR ; Microscopy, Confocal ; Motor Activity/physiology ; Neuroglia/cytology ; Neuroglia/metabolism ; Neuroglia/physiology ; Time Factors ; Vascular Endothelial Growth Factor A/metabolism
Keywords
angiogenesis ; astrocytes ; enriched environment ; hypoxic-ischemic brain injury ; mesenchymal stem cells
Abstract
Transplantation of mesenchymal stem cells (MSCs) has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE) in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O₂ for 90 min). At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS)-control (CON), PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.
Files in This Item:
T201603537.pdf Download
DOI
10.3390/ijms17091550
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
Yu, Ji Hea(유지혜)
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151989
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