Platelets Boost Recruitment of CD133 + Bone Marrow Stem Cells to Endothelium and the Rodent Liver-The Role of P-Selectin/PSGL-1 Interactions

• Published in: International journal of molecular sciences Vol. 21; no. 17; p. 6431
• Main Authors: Lehwald, Nadja, Duhme, Constanze, Pinchuk, Iryna, Kirchner, Julian, Wieferich, Kristina, Schmelzle, Moritz, Jurk, Kerstin, Windmöller, Beatrice A, Hübner, Wolfgang, Homey, Bernhard, Bode, Johannes, Kubitz, Ralf, Benhidjeb, Tahar, Krüger, Martin, Robson, Simon C, Knoefel, Wolfram T, Kehrel, Beate E, Schulte Am Esch, Jan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.09.2020; MDPI
• Subjects: AC133 Antigen - metabolism; Adhesion; Animals; Blood Platelets - physiology; Bone marrow; bone marrow stem cells; CD133; CD31 antigen; Cell culture; Confocal microscopy; CXCR4 protein; Endothelial cells; Endothelium; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Hepatocytes; Homing; Ischemia; Ligands; Liver; Liver - cytology; Liver - metabolism; liver regeneration; Localization; Male; Membrane Glycoproteins - metabolism; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Microscopy; P-selectin; P-Selectin - metabolism; P-selectin glycoprotein ligand 1; Perfusion; platelets; Rats; Rats, Wistar; Regeneration; SDF-1 protein; Shear stress; Stem cell transplantation; Stem cells; bone marrow stem cells; endothelial cells; liver regeneration; P-selectin; platelets; CD133
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176431

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.