Development of a potency assay for CD34 cell-based therapy.
Fiche publication
Date publication
novembre 2023
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LAHLIL Rachid
Tous les auteurs :
Aries A, Vignon C, Zanetti C, Goubaud A, Cormier A, Diederichs A, Lahlil R, Hénon P, Garitaonandia I
Lien Pubmed
Résumé
We have previously shown that intracardiac delivery of autologous CD34 cells after acute myocardial infarction (AMI) is safe and leads to long term improvement. We are now conducting a multicenter, randomized, controlled Phase I/IIb study in post-AMI to investigate the safety and efficacy of intramyocardial injection of expanded autologous CD34 cells (ProtheraCytes) (NCT02669810). Here, we conducted a series of in vitro studies characterizing the growth factor secretion, exosome secretion, gene expression, cell surface markers, differentiation potential, and angiogenic potential of ProtheraCytes clinical batches to develop a potency assay. We show that ProtheraCytes secrete vascular endothelial growth factor (VEGF) and its concentration is significantly correlated with the number of CD34 cells obtained after expansion. ProtheraCytes also secrete exosomes containing proangiogenic miRNAs (126, 130a, 378, 26a), antiapoptotic miRNAs (21 and 146a), antifibrotic miRNAs (133a, 24, 29b, 132), and miRNAs promoting myocardial regeneration (199a and 590). We also show that ProtheraCytes have in vitro angiogenic activity, express surface markers of endothelial progenitor cells, and can differentiate in vitro into endothelial cells. After the in vitro characterization of multiple ProtheraCytes clinical batches, we established that measuring the concentration of VEGF provided the most practical, reliable, and consistent potency assay.
Mots clés
Humans, Vascular Endothelial Growth Factor A, metabolism, Antigens, CD34, metabolism, MicroRNAs, metabolism, Myocardial Infarction, metabolism, Endothelial Progenitor Cells, metabolism, Neovascularization, Physiologic
Référence
Sci Rep. 2023 11 11;13(1):19665