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Open AccessArticle

Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies

1
Laboratoire d’Hépatologie Pédiatrique et Thérapie Cellulaire, Unité PEDI, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium
2
Promethera Biosciences, 1435 Mont-Saint-Guibert, Belgium
3
Unité CELL, Institut de Duve, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium
4
Unité d’Hémostase, Département des Laboratoires Cliniques, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
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Service d’Hépato-Gastroentérologie, Département de Médecine Interne, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
6
Services des Soins Intensifs, Département de Médecine Aigue, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
7
Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium
8
Service d’Anatomopathologie, Département des Laboratoires Cliniques, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
9
Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, 6211 LK Maastricht, The Netherlands
10
Institute for Molecular Cardiovascular Research (IMCAR), University Hospital Aachen, RWTH Aachen University, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 846; https://doi.org/10.3390/cells8080846
Received: 4 July 2019 / Revised: 3 August 2019 / Accepted: 6 August 2019 / Published: 7 August 2019
(This article belongs to the Special Issue Recent Advances in Liver Repair Strategies)
The efficacy of mesenchymal stem cell infusion is currently tested in numerous clinical trials. However, therapy-induced thrombotic consequences have been reported in several patients. The aim of this study was to optimize protocols for heterologous human adult liver-derived progenitor cell (HHALPC) infusion, in order to eliminate acute thrombogenesis in liver-based metabolic or acute decompensated cirrhotic (ADC) patients. In rats, thrombotic effects were absent when HHALPCs were infused at low cell dose (5 × 106 cells/kg), or at high cell dose (5 × 107 cells/kg) when combined with anticoagulants. When HHALPCs were exposed to human blood in a whole blood perfusion assay, blocking of the tissue factor (TF) coagulation pathway suppressed fibrin generation and platelet activation. In a Chandler tubing loop model, HHALPCs induced less explosive activation of coagulation with blood from ADC patients, when compared to blood from healthy controls, without alterations in coagulation factor levels other than fibrinogen. These studies confirm a link between TF and thrombogenesis, when TF-expressing cells are exposed to human blood. This phenomenon however, could be controlled using either a low, or a high cell dose combined with anticoagulants. In clinical practice, this points to the suitability of a low HHALPC dose infusion to cirrhotic patients, provided that platelet and fibrinogen levels are monitored. View Full-Text
Keywords: cell- and tissue-based therapy; liver transplantation; mesenchymal stem cells; thrombosis; anticoagulants cell- and tissue-based therapy; liver transplantation; mesenchymal stem cells; thrombosis; anticoagulants
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Coppin, L.; Najimi, M.; Bodart, J.; Rouchon, M.-S.; van der Smissen, P.; Eeckhoudt, S.; Dahlqvist, G.; Castanares-Zapatero, D.; Komuta, M.; Brouns, S.L.; Baaten, C.C.; Heemskerk, J.W.M.; Horman, S.; Belmonte, N.; Sokal, E.; Stéphenne, X. Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies. Cells 2019, 8, 846.

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