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

Louise Coppin*, Mustapha Najimi, Julie Bodart, Marie-Sophie Rouchon, Patrick van der Smissen, Stephane Eeckhoudt, Geraldine Dahlqvist, Diego Castanares-Zapatero, Mina Komuta, Sanne L. Brouns, Constance C. Baaten, Johan W. M. Heemskerk, Sandrine Horman, Nathalie Belmonte, Etienne Sokal, Xavier Stephenne

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Article number846
Number of pages16
JournalCells
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 2019

Keywords

  • cell- and tissue-based therapy
  • liver transplantation
  • mesenchymal stem cells
  • thrombosis
  • anticoagulants
  • STEM-CELLS
  • PROCOAGULANT ACTIVITY
  • TISSUE FACTOR
  • BONE-MARROW
  • THROMBUS FORMATION
  • ACUTE DECOMPENSATION
  • TRANSPLANTATION
  • DISEASE
  • FAILURE
  • SAFETY

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