January 2022

2018 Call: Recombinant laminin-like proteins for organoid cultures free of animal-derived basement membrane extract

Project OC-2018-004

Organoids are miniature organs generated from stem cells that provide unique in vitro models of organs in health and disease, and hold promises for personalized medicine and tissue engineering. They alleviate the need for animal experiments, as they enable the study of biomedical questions directly in vitro. They have become a cornerstone of 21st century biomedical research, and they still constitute a fast-developing field. In many cases, the tissue responsible for the organ-specific function – the parenchyma – is an epithelium, supported by a specialized matrix called a basement membrane. Examples include the intestine, liver, pancreas, kidney, lung, blood vessels, and skin. The brain also develops from neuroepithelium. Researchers have relied on basement membrane extract (BME) as a 3D matrix for their organoid cultures. BME is currently prepared from so-called Engelbreth-Holm-Swarm (EHS) tumours grown subcutaneously in mice. There is a strong need to develop BME alternatives, which avoid the use of mice, while simultaneously facilitating upscaling and clinical translation. We previously introduced alternative hydrogels that provide optimal physical properties: one based on the synthetic polymer poly(ethylene glycol) (PEG) and another based on the surgical tissue sealant fibrin Unfortunately, one last critical bioactive component, laminin, still needs to be purified from the BME, and has proven very challenging to replace. Here we propose to design and produce recombinant laminin fragments that retain the structure and function of the native protein while being easy to anchor to engineered matrices and amenable to mass-production.

Prof. Matthias Lütolf 
EPFL, matthias.lutolf@epfl.ch

Co-applicants: Nicolas Broguière, EPFL; Gerald Schwank, ETHZ