Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1ß and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage.
Cytotherapy
; 16(4): 523-34, 2014 Apr.
Article
de En
| MEDLINE
| ID: mdl-24424266
ABSTRACT
BACKGROUND AIMS:
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-1ß 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-1ß 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.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules souches
/
Hémorragie cérébrale
/
Facteur de nécrose tumorale alpha
/
Matrix metalloproteinase 12
/
Interleukine-1 bêta
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cytotherapy
Sujet du journal:
TERAPEUTICA
Année:
2014
Type de document:
Article