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Environmental Enrichment Synergistically Improves Functional Recovery by Transplanted Adipose Stem Cells in Chronic Hypoxic-Ischemic Brain Injury

 Seo, Jung Hwa  ;   Kim, Hyongbum  ;   Park, Eun Sook  ;   Lee, Jong Eun  ;   Kim, Dong Wook  ;   Kim, Hyun Ok  ;   Im, Sang Hee  ;   Yu, Ji Hea  ;   Kim, Ji Yeon  ;   Lee, Min-Young  ;   Kim, Chul Hoon  ;   Cho, Sung-Rae 
 CELL TRANSPLANTATION, Vol.22(9) : 1553-1568, 2013 
Journal Title
Issue Date
Adipose Tissue/cytology* ; Adipose Tissue/physiopathology ; Adipose Tissue/transplantation* ; Aged ; Animals ; Behavior, Animal/physiology ; Cell Differentiation/physiology ; Cells, Cultured ; Disease Models, Animal ; Environment* ; Female ; Humans ; Hypoxia-Ischemia, Brain/pathology ; Hypoxia-Ischemia, Brain/surgery ; Hypoxia-Ischemia, Brain/therapy* ; Male ; Mice ; Mice, Inbred ICR ; Neurogenesis/drug effects ; Recovery of Function ; Stem Cell Transplantation/methods*
Environmental enrichment (EE) ; Adipose stem cells (ASCs) ; Cell transplantation ; Neurogenesis ; Astrocyte ; Fibroblast growth factor 2 (FGF2)
We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5025-1532
Kim, Ji Yeon(김지연)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Park, Eun Sook(박은숙) ORCID logo https://orcid.org/0000-0002-9144-3063
Seo, Jung Hwa(서정화)
Yu, Ji Hea(유지혜)
Lee, Min Young(이민영)
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Im, Sang Hee(임상희) ORCID logo https://orcid.org/0000-0001-5128-5526
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
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