Developing defined substrates for stem cell culture and differentiation
Open accessAbstract
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’.
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ECM glycoproteins, like laminin, fibronectin, vitronectin or collagen, mediate stem cell adhesion, pluripotency maintenance, lineage commitment, migration, and neural differentiation through integrin signaling and biomechanical cues.
“ECM glycoproteins, like laminin, fibronectin, vitronectin or collagen, mediate stem cell adhesion, pluripotency maintenance, lineage commitment, migration, and neural differentiation through integrin signaling and biomechanical cues (Watt and Huck, 2013; Theocharis et al., 2016; Hagbard et al., 2018).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Hagbard et al., 2018
The ECM section says these molecules support adhesion and phenotype maintenance, and that laminin–integrin interactions regulate differentiation and migration. The sections on PSC maintenance and dopamine progenitors also describe laminin-supported self-renewal and neural differentiation. The paper discusses three-dimensional structure and cell orientation, but the passages do not establish biomechanical cues as a mechanism for the full set of effects claimed; the detailed integrin account concerns laminins rather than every listed glycoprotein. Page numbers are unavailable in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMany synthetic hydrogels require the incorporation of biochemical cues such as cell-binding peptides.
“First, many synthetic hydrogels require the incorporation of biochemical cues such as cell-binding peptides.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [181]
In the absence of biochemical cues cells may not attach to the hydrogel, leading to anoikis instead of organoid formation.
“In the absence of biochemical cues cells may not attach to the hydrogel, leading to anoikis (a type of programmed cell death)181 instead of organoid formation162.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [181]
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- Authors
- Hagbard, L., Cameron, K., August, P., Penton, C., Parmar, M., Hay, D. C., & Kallur, T.
- Affiliations
- BioLamina (Sweden) (SE)
- MRC Centre for Regenerative Medicine (GB)
- Icagen, Discovery Biology, Tucson Innovation Center, Oro Valley, AZ 85755, USA
- Lund University (SE)
- Corresponding author
- Kallur, Therése
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2018-05-21
- Volume
- 373
- Issue
- 1750
- Pages
- 20170230
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC5974452
- OpenAlex
- W2803504081
- Cited by
- 62
- References
- 70
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 4
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Eurostars-2 Joint Programme with co-funding from the European Union's Horizon 2020 research and innovation programme
- VINNOVA (2014-04086)
- MR (L022974/1)
- UKRMP MR (K026666/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- stem cell culture, stem cell differentiation, extracellular matrix, cell-matrix interactions, laminin, pluripotency, cell fate specification, cell therapy, cell niche, cell therapy manufacturing
- MeSH terms
- Cell Differentiation, Extracellular Matrix, Humans, Laminin, Stem Cells, Cell Culture Techniques
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