| First Author | Donndorf P | Year | 2017 |
| Journal | Microvasc Res | Volume | 112 |
| Pages | 87-92 | PubMed ID | 28363496 |
| Mgi Jnum | J:312170 | Mgi Id | MGI:6783337 |
| Doi | 10.1016/j.mvr.2017.03.011 | Citation | Donndorf P, et al. (2017) 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 |
| abstractText | 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/mm(2) in Control vs. 30.2+/-10.1cells/mm(2) 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/mm(2) in IR vs. 16.3+/-3.9cells/mm(2) in IR-TLR-2-ko vs. 14.5+/-4.4cells/mm(2) 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/mm(2) in IR-MyD88-ko vs. 30.1+/-9.9cells/mm(2) 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. |
