TY - JOUR
T1 - Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies
AU - Coppin, Louise
AU - Najimi, Mustapha
AU - Bodart, Julie
AU - Rouchon, Marie-Sophie
AU - van der Smissen, Patrick
AU - Eeckhoudt, Stephane
AU - Dahlqvist, Geraldine
AU - Castanares-Zapatero, Diego
AU - Komuta, Mina
AU - Brouns, Sanne L.
AU - Baaten, Constance C.
AU - Heemskerk, Johan W. M.
AU - Horman, Sandrine
AU - Belmonte, Nathalie
AU - Sokal, Etienne
AU - Stephenne, Xavier
PY - 2019/8
Y1 - 2019/8
N2 - 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 x 10(6) cells/kg), or at high cell dose (5 x 10(7) 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.
AB - 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 x 10(6) cells/kg), or at high cell dose (5 x 10(7) 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.
KW - cell- and tissue-based therapy
KW - liver transplantation
KW - mesenchymal stem cells
KW - thrombosis
KW - anticoagulants
KW - STEM-CELLS
KW - PROCOAGULANT ACTIVITY
KW - TISSUE FACTOR
KW - BONE-MARROW
KW - THROMBUS FORMATION
KW - ACUTE DECOMPENSATION
KW - TRANSPLANTATION
KW - DISEASE
KW - FAILURE
KW - SAFETY
U2 - 10.3390/cells8080846
DO - 10.3390/cells8080846
M3 - Article
C2 - 31394759
VL - 8
JO - Cells
JF - Cells
SN - 2073-4409
IS - 8
M1 - 846
ER -