title: Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1β and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage.
abstract: OBJECTIVE
  The molecular mechanisms by which stem cell transplantation improves functional recovery after intracerebral hemorrhage (ICH) are not well understood. Accumulating evidence suggests that microglia cells are activated shortly after ICH and that this activation contributes to secondary ICH-induced brain injury. We studied the effect of human amniotic epithelial stem cells (HAESCs) on microglia activation.
  
  
  METHODS
  To study the effect of HAESCs in vitro, we used thrombin to activate the microglia cells. Twenty-four hours after thrombin treatment, the levels of tumor necrosis factor-α and interleukin-1β were measured by enzyme-linked immunosorbent assay. In vivo, the HAESCs were transplanted into the rat striatum 1 day after collagenase-induced ICH. The expression levels of matrix metalloproteinase (MMP)-12 and microglia infiltration in the peri-hematoma tissues were determined 7 days after ICH through the use of reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively.
  
  
  RESULTS
  Thrombin-activated microglia expression of tumor necrosis factor-α, interleukin-1β and MMP-12 was significantly reduced through contact-dependent and paracrine mechanisms when the HAESCs were co-cultured with microglia cells. After transplantation of HAESCs in rat brains, the expression levels of MMP-12 and microglia infiltration in the peri-hematoma tissues were significantly reduced.
  
  
  CONCLUSIONS
  Our observations suggest that microglia activation could be inhibited by HAESCs both in vitro and in vivo, which may be an important mechanism by which the transplantation of HAESCs reduces brain edema and ameliorates the neurologic deficits after ICH. Therefore, we hypothesize that methods for suppressing the activation of microglia and reducing the inflammatory response can be used for designing effective treatment strategies for ICH.
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, Qingdao Hiser Medical Group, Qingdao, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Guan
authors.affiliation: School of Life Science, Northeast Agricultural University, Harbin, People's Republic of China.
authors.forename: Aili
authors.initials: A
authors.lastname: Gao
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Jing
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Enxi
authors.initials: E
authors.lastname: Hu
authors.affiliation: Key Laboratory of Neurosurgery, College of Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. Electronic address: Xiangtongzhang@Gmail.com.
authors.forename: Xiangtong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000628:therapy*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis*; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis*; D017628:Microglia / Q000378:metabolism / Q000637:transplantation; D019899:Paracrine Communication; D051381:Rats; D013234:Stem Cells / Q000166:cytology*; D013917:Thrombin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12
keywords: human amniotic epithelial stem cells; inflammation; intracerebral hemorrhage; microglia activation