Biography
Biography: Claire Saucourt
Abstract
Background: We previously demonstrated that intra-cardiac delivery of autologous peripheral blood-CD34+ stem cells, 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 ATMP (Advanced Therapy Medicinal Product). We have industrialized their production by developing an automated device for ex-vivo CD34+ stem cell expansion, starting from a whole blood sample. Method: Blood samples were collected from healthy donors after G-CSF mobilization. Manufacturing procedures included: (1) isolation of total nuclear cells (2) CD34+ immunoselection (3) expansion and cell culture recovery in the device and (4) expanded CD34+cell immunoselection and formulation. The assessment of CD34+ cell counts, viability and immunophenotype and sterility tests were performed as quality tests. Result: We established graft acceptance criteria and performed validation processes in three cell therapy centers (CTCs). 59.4±36.8×106 viable CD34+ cells were reproducibly generated as the final product from 220 mL whole blood containing 17.1±8.1x106 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 AMI (Acute Myocardial Infarct) in immuno-deficient rats during pre-clinical studies. Discussion: 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.