Advancing Animal-Free Research: A New Database for Basement Membrane Extract Alternatives Launches 

Utrecht University

The 3Rs Centre Utrecht has recently launched a new resource: the Basement Membrane Extract-free Database. This freely accessible platform, which provides a curated list of defined, animal-free alternatives to traditional basement membrane extract (BME), aims to support the transition toward more ethical and reproducible research practices. 

What is Basement Membrane Extract (BME)?  

Better known under the trade names Matrigel™, Cultrex™, or Geltrex™, BMEs are widely used for 2D and 3D cell culture applications. These complex mixture of extracellular matrix (ECM) proteins closely mimic the natural extracellular environment cells experience in body. BMEs have been a staple in scientific research for over 40 years. They are widely used to support 3D cell culture (organoids and spheroids) and in the culture and differentiation of pluripotent stem cells.

BME is an Animal-derived Biomaterial  

The production of BME raises significant ethical concerns. It is typically sourced from mouse tumour cells (Engelbreth-Holm-Swarm sarcoma), which secrete large amounts of basement membrane proteins. To obtain just 10 mL of BME, two purpose-bred mice are used. These animals are injected with tumour cells and sacrificed once the tumours have grown large enough to harvest the necessary proteins.  

The Limitations of BME  

While BME has been shown to support key cellular functions such as growth and differentiation it is a poorly defined mixture of proteins, which can vary greatly within a single batch and between batches. This leads to variation in both mechanical and biomechanical properties which undermines experimental reproducibility. For example, proteomic analyses of Matrigel have revealed inconsistent protein profiles: some studies detected important signalling molecules like insulin-like growth factor 1 and epidermal growth factor, while others failed to identify these proteins in multiple independent batches. Furthermore, the presence of biologically active proteins, including growth factors, can lead to unpredictable cellular responses.  Viral contaminants, such as lactate dehydrogenase-elevating virus, (LDHV) have also been found in several batches of animal-derived ECM products, including Matrigel.1 

What are the Alternatives?  

Recent innovations in synthetic scaffold technologies have produced chemically defined, xenogen-free alternatives. These new materials are highly tuneable, reproducible, and capable of directing specific cellular behaviours, while eliminating the unwanted effects associated with animal-derived matrices. 

The Importance of the Basement Membrane Extract-free Database

Despite the advancements in alternatives, BMEs remain in widespread use due to their commercial availability, ease of handling, and broad applicability across cell types. To support the transition toward more ethical and reproducible research practices, the 3Rs Centre Utrecht has launched a new resource: the Basement Membrane Extract-free Database. This freely accessible platform provides a curated list of defined, animal-free alternatives to traditional BME. It features a wide selection of matrices that promote cell growth and differentiation in both 2D and 3D models, supporting researchers in reducing animal use in cell culture and organoid studies. 

To raise awareness of the limitations of animal-derived BME and highlight the benefits of defined, animal-free options, the 3Rs Centre have launched a weekly LinkedIn campaign which started on 6th May. Each post will focus on a key reason to make the switch.

Empowering Researchers to Adopt Animal-free Alternatives

By empowering researchers with accessible, animal-free alternatives, much like the Foetal Calf Serum-free Database and the Centre for Human Specific Research’s recently launched Recombinant Antibodies & Mimetics Database, the BME-Free Database marks an important step toward more reproducible, human-specific and ethical biomedical science. 

References

  1. Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020 Jul;5(7):539-551. doi: 10.1038/s41578-020-0199-8. Epub 2020 May 27. PMID: 32953138; PMCID: PMC7500703.