Abstract: Cells within tissues interact directly with an extracellular matrix (ECM), a protein-rich framework essential for cellular adhesion, proliferation, differentiation, and maturation. The ECM family of laminins is composed of 16 different isoforms all critical for heathy tissue development and homeostasis. The laminin isoforms vary in expression both temporally and spatially, and act as active part in both the stem cell niches and differentiation.
The successful recapitulation of in vivo laminin expression has been demonstrated in various neural applications. For example, groundbreaking work by Kirkeby et al. (2016), which demonstrated the use of Biolaminin 521 and -111 to significantly enhance and standardize protocols for PSC-derived dopaminergic neurons. This approach increased cell yield by over 40-fold and facilitated clinical translation, setting a new benchmark for neural differentiation protocols. Biolaminin-111 and -521 have also been shown to enhance neural differentiation and reduce neuroinflammation in human 3D brain organoids (Bae et al., 2024), enabling long-term functional midbrain and cerebral organoid generation (Fiorenzano et al., 2021; Sozzi et al., 2022).
Here we demonstrate that Biolaminin 521 can support PSC-derived neural crest differentiation with high purity and yield. The monolayer culture simplifies the differentiation with equivalent or better result compared to the often-used aggregate differentiation. We further demonstrate that Biolaminin 521 in combination with -221 can support PSC-derived astrocyte differentiation, increase standardisation and accelerate differentiation, shortening the protocol with up to one week.
In conclusion, in vitro recapitulation of the natural cell niches, with recombinant laminin proteins, can lead to increased yield of desired target cells, simplified and accelerated protocols, as well as enabling clinical translation.
.jpg "Evan L. Lee Graham, PhD (he/him/his) photo")