Abstract
Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell–matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.
Highlights
Following the derivation of human embryonic stem cells in 1998 [1], and with the development of human induced pluripotent stem cells in 2007 [2,3], stem cell research is rapidly progressing from pre-clinical studies to the clinical arena with the first human trials having already begun
Current practices for the maintenance and expansion of undifferentiated human pluripotent stem cells typically depend on the support of undefined culture systems, such as feeder cells or undefined basement membrane (BM) extracts such as MatrigelTM and Geltrexw containing laminin-111, entactin, collagen, heparin sulfate proteoglycans and growth factors purified from Engelbreth– Holm– Swarm mouse sarcoma
Besides the risk of transmitting pathogens and the introduction of tumour-derived growth factors, culture conditions that depend on these undefined support systems limit experimental reproducibility and the ability to interpret mechanistic studies owing to lot-to-lot variations
Summary
Following the derivation of human embryonic stem cells (hESCs) in 1998 [1], and with the development of human induced pluripotent stem cells (hiPSCs) in 2007 [2,3], stem cell research is rapidly progressing from pre-clinical studies to the clinical arena with the first human trials having already begun. Besides the risk of transmitting pathogens and the introduction of tumour-derived growth factors, culture conditions that depend on these undefined support systems limit experimental reproducibility and the ability to interpret mechanistic studies owing to lot-to-lot variations. They hinder the transition of hPSC-derived products into a clinical setting. Compared with many other feeder-free matrices on the market, full-length laminin-521 better mimics the natural environment for hPSCs in culture [7,8,12] Owing to their biologically relevant interactions with cells, laminin-based substrates have significantly advanced the stem cell research field and are, the focus of this article. Laminins have become a preferred cell culture substrate both within basic research as well as for researches and companies with a therapeutic focus [13]
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