OC 75.5 - Platelet release device: From bench-scale to large culture platelet production

Wednesday, July 13, 2022

11:15 AM – 11:30 AM

Location: ExCel Center, ICC Capital Suite Room 10&11

Presentation Format: In-Person

Presenting Author(s)

Anaïs Pongerard

PhD Student
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France

Co-Author(s)

Léa Mallo, BSc

Engineer
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France
VD

Valentin Do Sacramento

PhD
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France
OB

Olivier Boiron

PhD
CNRS, Université Aix-Marseille, Ecole Centrale Marseille, IRPHE UMR7342, F-13000 Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
FL

François Lanza

PhD
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France
CG

Christian GACHET

MD/PhD
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France
Yannick KNAPP, PhD

Assistant Professor
Université Avignon, LAPEC UPR4278, F-84000 Avignon, France
Avignon, Provence-Alpes-Cote d'Azur, France
CS

Catherine Strassel

PhD
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France

Background: Platelet production is now feasible on a bench, but the remaining challenge is to move towards industrial production to enable clinical use. One way to achieve this goal is through the development of platelet release devices capable of producing bonafide platelets, at a high rate and in compliance with Good Manufacturing Practice.

Aims: Our study focused on the development of a platelet release device compatible with industrial requirements, allowing the production of important amounts of high quality cultured platelets.

Methods: From an analysis of flow generated during an established method of platelet release based on successive standard pipette up and down cycles, we designed a large-scale platelet release device compatible with industrial constraints, examined its main parameters and studied the quality of the released platelets.

Results: The device is composed of a succession of 5 spheres, each containing two calibrated cones placed in a staggered pattern matching the dimensions used during manual pipetting. Computational flow dynamics analysis showed the generation of periodic unsteady flows. Placed in negative pressure, this device allows the continuous flow of large volumes of culture (100 mL/min) and elevated platelet yields (100 platelets per megakaryocyte). Analysis of platelet morphology by electron microscopy showed that these platelets exhibit similar features than native ones despite their larger size (5.60 µm ± 0.52 diameter culture platelets vs 2.46µm ± 0.55 diameter native platelets). They are discoid and express the key glycoproteins to ensure platelet functions. Functionally, cultured platelets are able to activate their GPIIb-IIIa in response to thrombin 1 U/mL. Finally, we observed that released platelets recirculate at a very high efficiency following transfusion into immunodeficient mice with a half-life 4.33 fold higher than native platelets.

Conclusion(s): We have developed a platelet release device that meets the requirements for the large-scale production of cultured platelets suited for transfusion.