Good Cell Culture Practice for stem cells and stem-cell-derived models

Abstract

SummaryThe first guidance on Good Cell Culture Practice (GCCP) dates back to 2005. This document expands this to include aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice that can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times. This includes recommendations for the documentation and reporting of culture conditions. It is intended as guidance to facilitate the generation of reliable data from cell culture systems, and is not intended to conflict with local or higher level legislation or regulatory requirements. It may not be possible to meet all recommendations in this guidance for practical, legal or other reasons. However, when it is necessary to divert from the principles of GCCP, the risk of decreasing the quality of work and the safety of laboratory staff should be addressed and any conclusions or alternative approaches justified. This workshop report is considered a first step toward a revised GCCP 2.0.

21st Century Cell Culture for 21st Century Toxicology

“…Not applying GCCP in laboratories significantly increases the risk of generating erroneous data, withdrawal of publications, loss of scientific reputation, failed patent applications, wasted resources, laboratory worker infections, and exposure of host institutes to legal liability. 69 Validation of cell models has pioneered such quality assurance, but much work still needs to be done to create a culture of evidence-based science. The 21st century cell culture technologies discussed here pose many challenges for this.…”

Genomic Stability Testing of Pluripotent Stem Cells

“…Culture systems are complex, and PSC lines are rarely maintained under consistent conditions throughout their entire existence. Exact causes of recurrent aberrations are still being investigated; however, good PSC culture practices have started to coalesce (Pamies et al., 2017). Factors reported to precipitate genomic change in PSCs include high‐density culture (Jacobs et al., 2016), enzymatic single‐cell passaging, and feeder‐free conditions (Garitaonandia et al., 2015).…”

“…Additionally, it may be prudent to perform whole‐genome assessment immediately prior to entering a critical or costly stage of a project that is dependent on PSC genomic stability. Targeted assays, such as FISH and qPCR, can be used to assess genome status every 5 to 10 passages (Pamies et al., 2017) during routine culturing of cells where if genomic change does occur, it is likely to be in the form of a recurrent aberration (Taapken et al., 2011). Individual test regimens should be customized based on specific circumstances, and resource investment into testing should be a function of the PSC application.…”

“…Individual test regimens should be customized based on specific circumstances, and resource investment into testing should be a function of the PSC application. Investigators should be aware of and refer to available testing guidelines for their domain of PSC use, such as research (Pamies et al., 2017; The International Stem Cell Banking Initiative, 2009) or clinical applications (Andrews et al., 2015; Sullivan et al., 2018). Characterization capability (e.g., testing frequency, limit of detection, range) can be scaled as needed, using the mechanisms described herein; capabilities should be increased in proportion to the application significance.…”

The Ascendance of Microphysiological Systems to Solve the Drug Testing Dilemma

“…Second, the generation of reliable, reproducible and robust data needs to be assured by the adherence to the rules of Good Cell Culture Practice [74], and the use of qualified cell and tissue sources. The improvement of existing models and assays toward a closer recapitulation of in vivo physiology was also recommended recently [75].…”