Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery.
Fiche publication
Date publication
janvier 2020
Journal
NPJ Regenerative medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BONNET Dominique
Tous les auteurs :
Fellous TG, Redpath AN, Fleischer MM, Gandhi S, Hartner SE, Newton MD, François M, Wong SP, Gowers KHC, Fahs AM, Possley DR, Bonnet D, Urquhart P, Nicolaou A, Baker KC, Rankin SM
Lien Pubmed
Résumé
Therapeutic approaches requiring the intravenous injection of autologous or allogeneic mesenchymal stromal cells (MSCs) are currently being evaluated for treatment of a range of diseases, including orthopaedic injuries. An alternative approach would be to mobilise endogenous MSCs into the blood, thereby reducing costs and obviating regulatory and technical hurdles associated with development of cell therapies. However, pharmacological tools for MSC mobilisation are currently lacking. Here we show that β3 adrenergic agonists (β3AR) in combination with a CXCR4 antagonist, AMD3100/Plerixafor, can mobilise MSCs into the blood in mice and rats. Mechanistically we show that reversal of the CXCL12 gradient across the bone marrow endothelium and local generation of endocannabinoids may both play a role in this process. Using a spine fusion model we provide evidence that this pharmacological strategy for MSC mobilisation enhances bone formation.
Mots clés
Mesenchymal stem cells, Preclinical research, Regeneration
Référence
NPJ Regen Med. 2020 ;5:3