4 July, 2022
Paper Cells (Basic Research)
CREATIO’S PAPER DESCRIBING A SIGNIFICANT REDUCTION OF GENOMIC INSTABILITY IN HUMAN STEM CELL LINES UNDER QUALITY MANAGEMENT SYSTEM (QMS) CONDITIONS PUBLISHED AT CELLS
Published this month at the prestigious journal Cells, the paper describes and compares existing genomic alterations in commonly used human embryonic stem cell (hESCs) and human induced pluripotent stem cell (hiPSCs) lines. More importantly, it demonstrates how the application of a Quality Management System (QMS) promotes genomic stabilisation across human pluripotent stem cell (hPSCs) lines, leading to high-quality and reproducible scientific results.
Stem cell research holds great promise in a broad range of fields including drug discovery, regenerative medicine, disease modelling and unravelling embryonic development mechanisms. Indeed, articles utilising hPSCs – compromising both hESCs and hiPSCs – have increased by 56-fold in the last 30 years. Unfortunately, this growth has not been matched with the standardisation of the in vitro protocols used. Suboptimal culture conditions limit the reproducibility of the results but more importantly, are linked to genomic alterations that can jeopardize clinical translation. For instance, the detection of new alterations caused the termination of the RIKEN trial in 2015, the first study using hiPSC cells to treat patients with age-related macular degeneration (AMD).
The scientific community is well aware of these alterations, even though only 1 out of 20 articles assessed the genomic integrity of the hPSCs used. In this article, researchers at Creatio used results from existing studies complemented with our own 5-year data (2017-21) to better understand how often these alterations appear and what are their implications. Furthermore, they investigated whether the implementation of the ISO9001:2015 was able to improve the quality of the data by reducing the amount of genomic alterations in hPSCs. By comparing an array-based Comparative Genomic Hybridisation (aCGH, with a resolution of 1kb) with a more affordable but less sensitive technique (G-banding, detects changes larger than 5 Mb), researchers searched for aberrations in 8 hESC and 11 hiPSC lines, before and after adaptation to the QMS.
Results seen at Cells showed that whilst overall hiPSCs acquired more mutations (2 times higher by passage 42 than hESCs) these were mostly non-pathogenic compared to the ones in hESCs. Over time, hiPSCs remained more stable than hESCs, making them better candidates for future research and clinical applications. Interestingly, once the QMS was used, the quality of the cell lines significantly improved: hPSCs had a 4-fold reduction in acquisition of potentially-pathogenic genomic alterations by passage 7. These observations reveal the need of implementing a QMS when working with hPSCs. This is of particular importance in fields where alternative human methods are required such as neurosciences, where animal models have not proven its value.
Francisco Molina, main author in the Cells paper noted that “this work offers a comprehensive view of the accumulations of alterations during prolonged hPSC culture and, for the first time, supports the need to standardise in vitro culture practices”. The Marie-Curie ASCTN-ITN Early Stage Researcher (ESR) candidate expects that the scientific community the importance of implementing QMS in laboratories performing hPSC research.
Creatio, the production facility in regenerative medicine, holds a strong translational ethos. Creatio staff understand the importance of early standardisation to ensure laboratory results can reach the clinic. Dr Josep M. Canals, Director of Creatio, noted that “if regenerative medicine aims to hold its promise to patients, more attention ought to be placed on the quality of the in vitro protocols used, something that has yet to be implemented in academic settings”.
Read the full article here:
Molina-Ruiz, F.J.; Introna, C.; Bombau, G.; Galofre, M.; Canals, J.M. Standardization of Cell Culture Conditions and Routine Genomic Screening under a Quality Management System Leads to Reduced Genomic Instability in hPSCs. Cells 2022, 11, 1984.