Peptones in Therapeutic Environment – PEPITE

PEPITE is the result of collaboration between UMR1197 and the SME Organotechnie. Its objective is to open a high added value market for Organotechnie peptones by integrating them into the production of stem cells and their secretion products, extracellular vesicles (EVs) in tissue therapy, the field of innovation of UMR1197. This synergistic approach will provide a breakthrough innovation to improve the safety and therapeutic efficacy of these products. PEPITE will select the best performing peptones by relying on an effective and multidisciplinary partnership: 1) UMR1197 manages clinical trials using stem cells and masters the related technical and regulatory constraints. In addition to its GMP production unit, it has pre-GMP laboratory dedicated to the validation of the steps required for clinical production. 2) Organotechnie develops and manufactures peptones used in diagnostics, cell culture and fermentation. It already manufactures clinical grade products intended for pharmacology and masters the associated constraints.
Peptones are water-soluble mixtures of polypeptides and amino acids formed by the partial hydrolysis of protein-rich, vegetable raw materials for this project. They are effective additives to cell culture, but they are not validated for the production of stem cells and their derivatives in tissue therapy.
Tissue therapy using mesenchymal stem cells (MSCs) is booming. The methods of isolation and amplification of MSCs must be efficient, reproducible and safe, but the additives currently used for cell culture are of animal origin (fetal calf serum (FCS) or human (human platelet lysate (hPL)) and present major obstacles: batch to batch variability, undefined composition and for hPL, high production costs and difficult supply.
Plant peptones are a very promising alternative to FCS and hPL for preparing tissue therapy products.
In addition, therapeutic MSCs present potential risks related to their dissemination outside the injection site or the appearance of potentially dangerous gene mutations in the long term. Their storage and transport to the patient's bed are also constraints. Based on the observation that the therapeutic effect of MSCs is based on their trophic action, replacing them with the products they secrete (EV) is being considered by many specialists. The EVs secreted by MSCs have a similar efficacy to the MSCs from which they are derived, they lack genomic DNA, are not (or not very) immunogenic and are easy to store and transport.
Both FCS and hPL contain large amounts of EV which need to be removed prior to the production of EV from MSC. Peptones, devoid of EV will greatly facilitate the production and purification of EV from MSC while reducing costs.
Finally, we will fractionate the peptones to analyze the effectiveness of the different sub-fractions and better define their peptide composition. The most active sub-fractions will constitute new products with high added value. This biochemical and functional characterization of peptones will provide a better understanding of their mechanisms of action.
Our project aims thanks to PEPITE peptones -1) to improve the safety and efficiency of the production of therapeutic MSCs, -2) to allow the industrial production of EVs for tissue therapy, at much more accessible costs for the economy of health.
It will promote the scientific ecosystem relating to MSCs and EVs in which the UMR1197 operates, with Organotechnie as an industrial and commercial partner. It will also be a springboard for setting up the GMP conditions necessary for the development of EV-based products intended for clinical use.