Environmental enrichment synergistically improves functional recovery by transplanted adipose stem cells in chronic hypoxic-ischemic brain injury

Jung Hwa Seo, Hyongbum Kim, Eun Sook Park, Jong Eun Lee, Dong Wook Kim, Hyun Ok Kim, Sang Hee Im, Ji Hea Yu, Ji Yeon Kim, Min Young Lee, Chul Hoon Kim, Sung Rae Cho

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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% 02 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 βill-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.

Original languageEnglish
Pages (from-to)1553-1568
Number of pages16
JournalCell transplantation
Volume22
Issue number9
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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