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

Nadja Lehwald; Constanze Duhme; Iryna Pinchuk; Julian Kirchner; Kristina Wieferich; Moritz Schmelzle; Kerstin Jurk; Beatrice A Windmöller; Wolfgang Hübner; Bernhard Homey; Johannes Bode; Ralf Kubitz; Tahar Benhidjeb; Martin Krüger; Simon C Robson; Wolfram T Knoefel; Beate E Kehrel; Jan Schulte Am Esch

doi:10.3390/ijms21176431

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

Int J Mol Sci. 2020 Sep 3;21(17):6431. doi: 10.3390/ijms21176431.

Authors

Nadja Lehwald¹, Constanze Duhme¹, Iryna Pinchuk¹, Julian Kirchner², Kristina Wieferich¹, Moritz Schmelzle³, Kerstin Jurk^{4

5}, Beatrice A Windmöller⁶, Wolfgang Hübner⁷, Bernhard Homey⁸, Johannes Bode⁹, Ralf Kubitz⁹, Tahar Benhidjeb¹⁰, Martin Krüger¹¹, Simon C Robson¹², Wolfram T Knoefel¹, Beate E Kehrel⁵, Jan Schulte Am Esch¹⁰

Affiliations

¹ Department of Surgery A, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
² Department of Diagnostic and Interventional Radiology, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
³ Department of Surgery, Charite, 10117 Berlin, Germany.
⁴ Center for Thrombosis and Hemostasis, Johannes Gutenberg-University, 55122 Mainz, Germany.
⁵ Department of Anesthesiology Intensive Care and Pain Medicine, Experimental and Clinical Hemostasis, University of Muenster, 48149 Muenster, Germany.
⁶ Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
⁷ Biomolecular Photonics, Department of Physics, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.
⁸ Department of Dermatology, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
⁹ Department of Gastroenterology, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
¹⁰ Center of Visceral Medicine, Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, 33617 Bielefeld, Germany.
¹¹ Center of Visceral Medicine, Department of Gastroenterology and Internal Medicine, Protestant Hospital of Bethel Foundation, 33617 Bielefeld, Germany.
¹² The Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA 02215, USA.

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.

Keywords: CD133; P-selectin; bone marrow stem cells; endothelial cells; liver regeneration; platelets.

MeSH terms

AC133 Antigen / metabolism*
Animals
Blood Platelets / physiology*
Endothelium, Vascular / cytology*
Endothelium, Vascular / metabolism
Liver / cytology*
Liver / metabolism
Male
Membrane Glycoproteins / metabolism*
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / metabolism
Mice
Mice, Inbred C57BL
P-Selectin / metabolism*
Rats
Rats, Wistar

Substances

AC133 Antigen
Membrane Glycoproteins
P-Selectin
P-selectin ligand protein

Abstract

MeSH terms

Substances

Grants and funding