Cell Biology

Quality control is a crucial and decisive factor for the appropriate use of human pluripotent stem cells and their derivatives. At I-Stem, we pay particular attention to this area of investigation, as undetected cellular abnormalities may lead to major errors in disease modeling and pharmacological studies or introduce significant safety risks in the context of cell therapy. For this reason, our team performs systematic and regular quality assessments of all cell lines generated within the Institute.

Karyotyping is used to detect chromosomal abnormalities ranging in size from approximately 5 to 10 Mb (megabases). This approach enables the identification of both balanced structural abnormalities, such as reciprocal translocations, and numerical chromosomal abnormalities, including trisomy and monosomy. To achieve this, we use conventional cytogenetic techniques, including G-banding and R-banding, as well as multicolor Fluorescence In Situ Hybridization (mFISH), allowing a comprehensive and accurate characterization of the cellular genome.

To further improve the assessment of genomic integrity, the platform maintains an active technology watch and continuously evaluates emerging detection methods. Through our collaboration with StemGenomics (Montpellier, France), we have access to a rapid screening assay capable of detecting the most frequently acquired genetic abnormalities in pluripotent stem cells. This tool represents an essential quality control step during critical activities, such as the generation of large-scale cell banks by the Bioproduction Platform or genome-editing procedures using CRISPR/Cas9 technology, thereby ensuring the integrity of the cells employed in these processes.

Over the past several years, the team has developed recognized expertise in these areas. Notable projects have included the investigation of immune-evasion mechanisms (“ghost cells”) in collaboration with the team of Thierry Heidmann, the company Viroxis, and the CR2TI research center in Nantes. The team has also participated in the MyoPharm program, through which I-Stem collaborated with several French research groups to develop innovative therapeutic approaches for ultra-rare neuromuscular disorders.

The platform also provides its expertise to academic and industrial partners through genetic and cytogenetic testing services, including karyotyping by G/R-banding and mFISH, as well as SNP-array analyses for the high-resolution detection of chromosomal abnormalities.

ANR AAPG 2021 – PRCE: Ghosting The Cells (GTC):

Research project focused on the generation of “ghost” cells that preserve normal HLA antigen presentation mechanisms while reducing immune recognition through the membrane display of a retrovirus-derived immunosuppressive molecule.