Calf-Free Research: Developing robust approaches to replace foetal calf serum with synthetic alternatives in cell culture

Manuela and the Crick’s cell services team will conduct a large-scale study to test five commercially available animal-free serum formulations on 50 different cell lines used by scientists from a range of disciplines. They will characterise and compare the effect of different serums on cellular morphology and behaviour – by building confidence for scientists working at the Institute and across their industry partners to switch to synthetic serum, the work could replace the use of over 1,900 calves each year.

This award was made as part of the 2024 non-animal derived product validation grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

This project, led by the Francis Crick Institute’s Cell Services Platform, focuses on evaluating the effects of commercially available non–animal-derived serum alternatives on cellular functions of a curated, large, and diverse library of established cell lines. The goal is to identify viable replacements for foetal calf serum (FCS), one of the most used supplements, to replace its usage in cell cultures towards more ethical research practices, better predictive models, and better intra- and inter-laboratory reproducibility.

Using advanced assays to evaluate morphological, proliferation and bioenergetic parameters, we will compare the performance of various serum substitutes against traditional FCS. We will establish reliable and robust transition protocols, evaluate ad-hoc optimizations on more demanding cell lines, and assess the impact of the transition to FCS alternatives on cell health, viability, and function.

This project aims to provide crucial information to the scientific community on the suitability of synthetic serum in the culture of a variety of cell lines. This will allow researchers to shift to the most appropriate commercially available, chemically defined serum alternatives with minimal risk to the integrity of their research.

Objectives:

1. Establish successful transition protocols from FCS to chemically defined sera on a large library of cells.
2. Evaluate cellular morphology, growth characteristics and bioenergetic profiles of successfully adapted cell lines.
3. In-depth analysis of a selected subset of cell lines to thoroughly assess their health, functionality, and overall performance.
4. Correlate performance metrics to cell type, disease, organ, species, and media and compare pre- to post-transition cells to understand the impact of the new conditions on cell health and function.

Significance:
This research supports the NC3Rs principles by seeking to replace animal-derived components in cell culture, thus advancing ethical and sustainable research practices. By proactively supporting the transition to non-animal derived serum alternatives, we aim to decrease the reliance on FCS and reduce the ethical concerns associated with its production, including animal distress, and environmental deterioration. Our goal is to provide the research community with viable alternatives for their cell culture needs. We expect that the findings from this study will bring valuable insights into how to transition to non-animal derived serum alternatives, and their impact on cellular function, allowing for more informed decisions about their use. This will ultimately alleviate concerns about these alternatives and foster more responsible and innovative research practices.