Growth factors, matrices, and forces combine and control stem cells

By Dennis E. Discher, David J. Mooney, P. Zandstra. Science, 2009

2,622 citations recorded by the source corpus.

Stem cell fate is influenced by a number of factors and interactions that require robust control for safe and effective regeneration of functional tissue. Coordinated interactions with soluble factors, other cells, and extracellular matrices define a local biochemical and mechanical niche with complex and dynamic regulation that stem cells sense. Decellularized tissue matrices and synthetic polymer niches are being used in the clinic, and they are also beginning to clarify fundamental aspects of how stem cells contribute to homeostasis and repair, for example, at sites of fibrosis. Multifaceted technologies are increasingly required to produce and interrogate cells ex vivo, to build predictive models, and, ultimately, to enhance stem cell integration in vivo for therapeutic benefit.

Subfields: Biomaterials, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/7d11ee48da7ad91b904743215274fac46a6666a6

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Citations in the corpus

Designing materials to direct stem-cell fate (2009, background): “In addition to understanding this biochemical signalling regulatory network, it is key to appreciate the biophysical properties of the niche, including matrix mechanical properties and architecture (topographical cues), to elucidate the role of niche element”
Nanocomposite hydrogels for biomedical applications (2013, background): “Over the last decade, new applications of hydrogels have emerged, particularly in stem cell engineering, immunomodulation, cellular and molecular therapies, and cancer research (Discher et al., 2009; Tibbitt and Anseth, 2009).”
The Hippo Signaling Pathway in Development and Disease (2019, background): “For example, cells grown on stiff ECM or spread across a large surface are also flat and show nuclear localization of YAP, while cells grown on soft ECM, on a small surface, or detached from a culture plate are round and show cytoplasmic YAP localization (Dupont et al., 2011; Wada et al., 2011; Zhao”
The biology of YAP/TAZ: hippo signaling and beyond. (2014, background): “Cell mechanics and the status of the cytoskeleton are true overarching signals that cells use to make essential decisions, such as proliferation, differentiation, and maintenance of stem cells (48, 95, 131, 225).”
Forces in tissue morphogenesis and patterning. (2013, neutral): “In particular, MSCs differentiate into osteoblasts on stiff ECM that mimics the natural bone environment, whereasMSCs differentiate in other lineages, such as adipocytes, on soft ECM (Discher et al., 2009).”
Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer (2011, neutral): “…arise from defects in bone marrow stroma that lead to an abnormal microenvironment, which is thought to contribute to tumorigenesis and drive tumor progression, providing an example of how ECM changes might promote non-epithelial malignancies (Dror and Freedman, 1999; Michigami et al., 2000).”
A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. (2013, neutral): “For organ size control, tissue regeneration, and homeostasis, cells must be constantly informed of the size and shape of the whole organ (Discher et al., 2009; Huang and Ingber, 1999; Nelson and Bissell, 2006).”
Natural Polymeric Scaffolds in Bone Regeneration (2020, background): “- Biodegradable - Slow degradation - Excellent mechanical properties - High thermal stability - High mechanical strength - Reduced availability (e.g. low production from spiders) - High brittleness - Residue contaminants (Shi et al., 2016; Kowalczewski and Saul, 2018) Hyaluronic acid - Highly biocom”
Highly stretchable and tough hydrogels (2012, background): “Hydrogels are used as scaffolds for tissue engineering [1], vehicles for drug delivery [2], actuators for optics and fluidics [3], and model extracellular matrices for biological studies [4].”