6533b861fe1ef96bd12c5770

RESEARCH PRODUCT

CD133+ bone marrow stem cells (BMSC) control platelet activation – Role of ectoNTPDase-1 (CD39)

Constanze DuhmeNadja LehwaldWolfram T. KnoefelMartin KrügerArlette NgepiEllen BauchrowitzJan Schulte Am EschMoritz SchmelzleTheodoros KolokotronisTahar BenhidjebKerstin JurkBeate E. KehrelSimon C. Robson

subject

Cell typeEndotheliumChemistryBone Marrow Stem CellCell BiologyHematologyLiver regenerationCell biologymedicine.anatomical_structuremedicineMolecular MedicinePlateletPlatelet activationStem cellMolecular BiologyHoming (hematopoietic)

description

Abstract Background We previously demonstrated CD133+ bone marrow stem cells (BMSC) to promote hepatic proliferation for liver regeneration. Here, we evaluated the capacity of CD133+BMSC to utilize platelets for homing to vasculature and concomitant controlling their aggregability upon ADP stimulation. Methods CD133+BMSC and platelets were co-cultured along micro endothelial cells under variable flow conditions and tested for homing levels along vasculature. Aggregometry and FACS analysis were utilized to evaluate platelet reactivity following co-incubation ± CD133+BMSC. RT-PCR and FACS analyses served to characterize ADP degrading ectonucleoside triphosphate diphosphohydrolase-1 (ectoNTPDase-1/CD39) expression on various cell types. Results Platelets attracted human CD133+BMSC to autologous micro endothelium under shear stress unaffected by ADP stimulation. However, CD133+BMSC inhibited ADP-mediated platelet activation and aggregation. Latter was dependent on ectoNTPDase-1 expression levels. Platelet aggregatory control was increased with CD133+BMSC compared to CD133+PHSC. Different effects of those stem cell subtypes positively correlated with their FACS-detected expression levels of ectoNTPDase-1. Conclusion We provide evidence that CD133+BMSC are capable of controlling ADP-dependent platelet aggregation and activation by direct interaction dependent on cellular expression of ectoNTPDase-1. Whether different capacities of BMSC modulate platelet-depending thrombogenicity at sites of regeneration impact effectiveness and adverse event profiles of regenerative treatment requires further evaluation.

https://doi.org/10.1016/j.bcmd.2019.04.012