| Autor: |
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 |
| Zdroj: |
Stem Cells Translational Medicine; August 2019, Vol. 8 Issue: 8 p822-832, 11p |
| Abstrakt: |
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 × 106± 36.8 × 106viable CD34+cells were reproducibly generated as the final product from 220 ml WB containing 17.1 × 106± 8.1 × 106viable 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 Medicine2019;8:822&832 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text