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

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Saucourt, Claire | Vogt, Sandrine | Merlin, Amandine | Valat, Christophe | Criquet, Anthony | Harmand, Laurence | Birebent, Brigitte | Rouard, Hélène | Himmelspach, Christian | Jeandidier, Éric | Chartois‐leauté, Anne‐gaële | Derenne, Sophie | Koehl, Laurence | Salem, Joe‐elie | Hulot, Jean‐sébastien | Tancredi, Céline | Aries, Anne | Judé, Sébastien | Martel, Eric | Richard, Serge | Douay, Luc | Hénon, Philippe

Edité par CCSD ; Wiley -

International audience. 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 6 AE 36.8 × 10 6 viable CD34 + cells were reproducibly generated as the final product from 220 ml WB containing 17.1 × 10 6 AE 8.1 × 10 6 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.

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