Abstract：
:We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligand-1 (PSGL-1). Inhibition of PECAM-1 as well as SDF-1 receptor CXCR4 had no such effect. In a model of the isolated reperfused rat liver subsequent to warm ischemia, the co-infusion of platelets augmented CD133+BMSC homing to the injured liver with heightened transmigration towards the extra sinusoidal space when compared to perfusion conditions without platelets. Extravascular co-localization of CD133+BMSC with hepatocytes was confirmed by confocal microscopy. We demonstrated an enhancing effect of platelets on CD133+BMSC homing to and transmigrating along hepatic EC putatively depending on PSGL-1 and P-selectin. Our insights suggest a new mechanism of platelets to augment stem cell dependent hepatic repair.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Lehwald N,Duhme C,Pinchuk I,Kirchner J,Wieferich K,Schmelzle M,Jurk K,Windmöller BA,Hübner W,Homey B,Bode J,Kubitz R,Benhidjeb T,Krüger M,Robson SC,Knoefel WT,Kehrel BE,Schulte Am Esch Jdoi
10.3390/ijms21176431subject
Has Abstractpub_date
2020-09-03 00:00:00issue
17issn
1422-0067pii
ijms21176431journal_volume
21pub_type
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