PLURIPOTENCY ENGINEERING -
Stem Cells & Organoïds
Joint lab Sup'Biotech / CEA-SEPIA (Service d'étude des prions et des infections atypiques)
Induced pluripotent stem cells (IPS) are potentially immortal cells, capable of proliferating indefinitely while maintaining a stable genetic heritage. They represent one of the most modern and innovative applications of cell biology, as they offer the prospect of an unlimited supply of human cells of all types. The IPS cell model is particularly suitable for cell engineering techniques, which consist in modifying the genome of cells in order to adapt their properties for the needs of industrial research. These cells can be used as a model for certain genetic disorders, but also as a source of innovative therapeutic strategies.
Thanks to the intrinsic self-organizing properties of pluripotent cells, it is possible to create "organoids" from these cells, i.e. three-dimensional structures that bring together certain characteristics of human organs. One of the problems of the CellTechs team is to study whether human neuroectodermal oragnoids (mini-brains) can represent a study model for certain neurodegenerative pathologies.
These technologies may provide a reliable pharmacological screening tool that goes beyond the limitations of the modeling tools currently used in the pharmaceutical industry.
In 2018, CellTechs acquired a light-sheet microscope capable of three-dimensional "scanning" biological samples such as organoids.
Cellular tool bank
The Sup'Biotech/CEA team also aims to develop, transfer and validate cellular models that are more relevant for the study of Alzheimer's disease and prion diseases or to promote them to researchers and industrialists. The cellular tools generated and validated in the laboratory will therefore be stored in a well characterized Master Cell Bank.
The industrial transfer of these technologies requires a particular effort in standardization and quality control of the different stages of cell culture. The adaptation of new techniques (imaging, automation, etc.) to the culture of pluripotent stem cells is a particularly important challenge for the industrial sector. Thanks to a network of international collaborations, the "Ingénierie de la Pluripotence" team maintains a technological watch on the most recent innovations in order to have access to cutting-edge applications in the field of cellular biotechnology.
Neurodegenerative diseases (Alzheimer's, Prion diseases, etc.): SEPIA's expertise in the field of in vivo modelling of these pathologies will be used to derive new in vitro models based on the use of pluripotent IPS cells.
Pluripotency engineering: new reprogramming and differentiation techniques are developed based on the unique tools derived at the SEPIA laboratory. These techniques will make it possible to obtain animal and human cellular models with high valuation potential.
Pavoni S., Jarray R., Nassor F., Guyot AC, Cottin S. Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotype" PlosOne, 2018 Dec 17;13(12):e0209150.
Mouka A, Izard V, Tachdjian G, Brisset S, Yates F, Mayeur A, Drévillon L, Jarray R, Leboulch P, Maouche-Chrétien L, Tosca L. "Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies". Sci Rep. 2017 Jan
Kobari L, Yates F, Oudrhiri N, Francina A, Kiger L, Mazurier C, Rouzbeh S, El-Nemer W, Hebert N, Giarratana MC, François S, Chapel A, Lapillonne H, Luton D, Bennaceur-Griscelli A, Douay L "https://www.ncbi.nlm.nih.gov/pubmed/28045072" Haematologica. 2012;97:1795-803.
Lirsac PN, Blin O, Magalon J; participants of round table N°5 of Giens XXX:, Angot P, de Barbeyrac E, Bilbault P, Bourg E, Damour O, Faure P, Ferry N, Garbil B, Larghero J, Nguon M, Pattou F, Thumelin S, Yates F. "Creating conditions for the success of the French industrial advanced therapy sector. Therapy. 2015 Jan-Feb;70(1):69-94.
Stagiaire (Biotech 4)
LightSheet Ultramicroscope II