Evaluation of Strategies Aimed at Improving Liver Progenitor Cell Rolling and Subsequent Adhesion to the Endothelium

Autor: Pierre Edouard Dollet, Mei Ju Hsu, Jérôme Ambroise, Milena Rozzi, Joachim Ravau, Floriane André, Jonathan Evraerts, Mustapha Najimi, Etienne Sokal, Catherine Lombard
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Transplantation, Vol 29 (2020)
Druh dokumentu: article
ISSN: 1555-3892
09636897
DOI: 10.1177/0963689720912707
Popis: Adult-derived human liver stem/progenitor cells (ADHLSCs) are a promising alternative to orthotopic liver transplantation in the treatment of inborn errors of metabolism. However, as is the case with many mesenchymal stromal cells, ADHLSCs have shown a low level of engraftment, which could be explained by the fact that they lack expression of selectin ligand and LFA-1 and only slightly express VLA- 4, molecules that have been shown to be involved in cell adhesion to the endothelium. In this paper, we have investigated strategies to increase their rolling and adhesion during the homing process by (1) adding a selectin ligand (Sialyl Lewis X) to their surface using biotinyl- N -hydroxy-succinimide–streptavidin bridges, and (2) protecting the adhesion proteins from trypsinization-induced damage using a thermosensitive polymer for cell culture and a nonenzymatic cell dissociation solution (CDS) for harvest. Despite increasing adhesion of ADHLSCs to E-selectin during an adhesion test in vitro performed under shear stress, the addition of Sialyl Lewis X did not increase adhesion to endothelial cells under the same conditions. Cultivating cells on a thermosensitive polymer and harvesting them with CDS increased their adhesion to endothelial cells under noninflammatory conditions, compared to the use of trypsin. However, we were not able to demonstrate any improvement in cell adhesion to the endothelium following culture on polymer and harvest with CDS, suggesting that alternative methods of improving engraftment still need to be evaluated.
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