Design and Validation of an Automated Process for the Expansion of Peripheral Blood-Derived CD34 Cells for Clinical Use After Myocardial Infarction.

Fiche publication

Date publication

avril 2019

Journal

Stem cells translational medicine

Auteurs

Membres identifiés du Cancéropôle Est :
Dr JEANDIDIER Eric

Tous les auteurs :
Saucourt C, Vogt S, Merlin A, Valat C, Criquet A, Harmand L, Birebent B, Rouard H, Himmelspach C, Jeandidier É, Chartois-Leauté AG, Derenne S, Koehl L, Salem JE, Hulot JS, Tancredi C, Aries A, Judé S, Martel E, Richard S, Douay L, Hénon P

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31037857

Résumé

We previously demonstrated that intracardiac delivery of autologous peripheral blood-derived CD34 stem cells (SCs), mobilized by granulocyte-colony stimulating factor (G-CSF) and collected by leukapheresis after myocardial infarction, structurally and functionally repaired the damaged myocardial area. When used for cardiac indication, CD34 cells are now considered as Advanced Therapy Medicinal Products (ATMPs). We have industrialized their production by developing an automated device for ex vivo CD34 -SC expansion, starting from a whole blood (WB) sample. Blood samples were collected from healthy donors after G-CSF mobilization. Manufacturing procedures included: (a) isolation of total nuclear cells, (b) CD34 immunoselection, (c) expansion and cell culture recovery in the device, and (d) expanded CD34 cell immunoselection and formulation. The assessment of CD34 cell counts, viability, and immunophenotype and sterility tests were performed as quality tests. We established graft acceptance criteria and performed validation processes in three cell therapy centers. 59.4 × 10 ± 36.8 × 10 viable CD34 cells were reproducibly generated as the final product from 220 ml WB containing 17.1 × 10 ± 8.1 × 10 viable CD34 cells. CD34 identity, genetic stability, and telomere length were consistent with those of basal CD34 cells. Gram staining and mycoplasma and endotoxin analyses were negative in all cases. We confirmed the therapeutic efficacy of both CD34 -cell categories in experimental acute myocardial infarct (AMI) in immunodeficient rats during preclinical studies. This reproducible, automated, and standardized expansion process produces high numbers of CD34 cells corresponding to the approved ATMP and paves the way for a phase I/IIb study in AMI, which is currently recruiting patients. Stem Cells Translational Medicine 2019.