Therapeutic progenitor cell application for tissue regeneration: Analyzing the impact of toll-like receptor signaling on c-kit+ cell migration following ischemia-reperfusion injury in vivo.
Microvasc Res
; 112: 87-92, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28363496
ABSTRACT
OBJECTIVES:
Toll-like-receptor (TLR) mediated immune response has been shown to regulate myocardial damage following cardiac ischemia-reperfusion (IR). It has not been described conclusively so far whether migration of therapeutically applied progenitor cells following an IR event depends on TLR-signaling.METHODS:
In vivo migratory capacity murine c-kit+ cells following IR injury was quantified by intravital fluorescence microscopy, utilizing the mouse cremaster muscle model and analyzing early (rolling) and late (adhesion) c-kit+ cell interaction with the local endothelium. The role of TLR-2 and TLR-4, as well as MyD88 and TRIF was analyzed by applying specific knock-out models.RESULTS:
A sequence of 15min ischemia followed by 15min of reperfusion induced firm endothelial c-kit+ cell adhesion (5.6±1.3cells/mm2 in Control vs. 30.2±10.1cells/mm2 in IR, p<0.05). Knock-out of TLR-2 and TLR-4 diminished both IR induced early c-kit+ cell-endothelial cell interactions (67.6±2.3% c-kit+ cell rolling in IR vs. 46.3±4.8% c-kit+ cell rolling in IR-TLR-2-ko vs. 45.3±4.8% c-kit+ cell rolling in IR-TLR-4-ko, p<0.05) as well as firm endothelial c-kit+ cell adhesion (30.2±10.1cells/mm2 in IR vs. 16.3±3.9cells/mm2 in IR-TLR-2-ko vs. 14.5±4.4cells/mm2 in IR-TLR-4-ko, p<0.05). Adaptor protein knock-out resulted in a significantly decreased firm endothelial c-kit+ cell adhesion only in MyD88 knock-out but not in TRIF knock-out (9.2±2.2cells/mm2 in IR-MyD88-ko vs. 30.1±9.9cells/mm2 in IR-WT, p<0.05).CONCLUSION:
Artificially applied c-kit+ cells interact with the target organ endothelium following IR injury. This interaction seems to depend on TLR-MyD88 signaling. Therapeutic blockade of TLR signaling for anti-inflammatory purposes might interfere with regenerative cell-based therapy protocols.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Células-Tronco
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Traumatismo por Reperfusão
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Movimento Celular
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Músculos Abdominais
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Proteínas Proto-Oncogênicas c-kit
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Transplante de Células-Tronco
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Receptor 2 Toll-Like
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Receptor 4 Toll-Like
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Microvasc Res
Ano de publicação:
2017
Tipo de documento:
Article