Biorelevant full-length Biolaminin 521 enhances primary MSCs proliferation and generation of iMSCs with stable expansion and differentiation potential

Abstract

Background & Aim

Mesenchymal stromal cells (MSCs) are powerful therapeutic tools in regenerative medicine. The functions of MSCs are tightly regulated by the interaction with their microenvironment, where survival and differentiation potential of MSCs is controlled by intrinsic mechano-signalling pathways. However, challenges remain such as source-heterogeneity and use of undefined and xenogenic culture conditions hampering standardization and clinical transition. Protocol adaptation to xenofree and chemically defined cell culture condition, suitable for both cell type and applications, is crucial for expanding their therapeutic potential. Laminins are a family of large extracellular matrix (ECM) proteins found throughout the body, essential for healthy tissue development- and tissue homeostasis, particularly abundant in basement membranes of epithelial- and endothelial tissues. Here, full-length laminins play a critical role in shaping the microenvironment and in mediating cell-ECM interactions via establishment of focal adhesion contacts. Their role is essential for stable cellular survival, identity, and migration. Biolaminin® s are full-length human recombinant laminin proteins, scientifically proven to support human pluripotent stem cells (PSC) and targeted differentiation in vitro, replacing tissue extract products. Biolaminin® 521 is particularly known to support PSCs and adult stem cells niches in vitro.

Methodology

Primary adipose derived-MSCs and induced PSC (iPSC)-derived mesenchymal stromal cells (iMSCs) were employed in these studies.

Results

Primary MSCs cultivated on Biolaminin® 521 maintain a stable- and fast proliferation compared to plastic (no coat) or other traditional substrates, also in serum-free conditions. Moreover, researchers have demonstrated that full-length Biolaminin 521 supports generation, expansion and differentiation of iMSCs. Biolaminin 521 supports stable and fast proliferation of iMSCs up to 10 passages compared to other substrates such as fragmented laminin and laminin-rich tissue extract products. Full-length laminin significantly increases mineral deposition of iMSCs-derived osteoblast inducing a uniform and efficient osteogenic differentiation over plastic or tissue extracts products.

Conclusion

In conclusion, Biolaminin 521 is a biologically relevant, xeno-free and defined substrate, enhancing primary MSCs proliferation and supporting iMSCs culture, from initial generation to downstream differentiation enabling protocol standardization and clinical translation.