Design and Validation of an Automated Process for the Expansion of Peripheral Blood-Derived CD34+ Cells for Clinical Use After Myocardial Infarction. (29th April 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Stem cells translational medicine. Volume 8:Number 8(2019)
• Page Start: 822
• Page End: 832
• Publication Date: 2019-04-29
• Subjects: CD34+ -- Cellular therapy -- Hematopoietic stem cells -- Peripheral blood stem cells -- Cardiac -- Cell culture; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.17-0277
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: 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 ± 36.8 × 10 6 viable CD34 + cells were reproducibly generated as the final product from 220 ml WB containing 17.1 × 10 6 ± 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. Stem Cells Translational Medicine 2019;8:822–832 : Abstract : This article presents a simplified and standardized production process yielding high amounts of CD34 + cells. After a phase of development, validation processes have been realized in three different cell therapy centers. Expanded CD34 + cells' characteristics were consistent with those of basal CD34 + cells. Those results, combined with those of a proof of concept study realized on rats, allowed us to begin the EXCELLENT phase I/IIb clinical trial.