Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix

Abstract

A diverse array of environmental factors contribute to the overall control of stem cell activity. In particular, new data continues to mount on the influence of the extracellular matrix (ECM) on stem cell fate through physical interactions with cells, such as the control of cell geometry, ECM geometry/topography at the nanoscale, ECM mechanical properties, and the transmission of mechanical or other biophysical factors to the cell. Here we review some of the physical processes by which cues from the ECM can influence stem cell fate, with particular relevance to the use of stem cells in tissue engineering and regenerative medicine.

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

“…At the mRNA level, ASCs seeded in ELP showed upregulated SOX9 and type II collagen gene expression, whereas type I collagen was downregulated. These findings provide additional evidence of the chondrogenic ability of ASCs and the ability of biomaterial scaffolds to directly control stem cell differentiation [35], even in the absence of exogenous growth factors [6].…”

“…In particular, findings suggest that a rounded cell shape (via threedimensional scaffolds or micromass culture) is a critical factor in the induction of the chondrogenic phenotype, and thus physical interactions with the extracellular matrix may have a significant effect on maintaining ASC phenotype over the long term [35]. This evidence suggests that it will be possible to exploit such mechanoinductive stimuli to modulate the chondrogenic differentiation and function of ASCs in conjunction with more traditional biochemical growth factors [38,51,54].…”

“…In addition to the biochemical interactions that scaffolds may have with cell surface receptors, there is growing evidence of the important role that physical interactions between stem cells and their extracellular matrix have in regulating stem cell fate [25,35]. One of the studies showed that different construct materials or structures can significantly influence the differentiation of ASCs and functional properties of the tissue-engineered construct [5].…”

Insights into the Role of Focal Adhesion Modulation in Myogenic Differentiation of Human Mesenchymal Stem Cells

“…U nderstanding cell-material interactions is pivotal in tissue engineering and regenerative medicine, to effectively direct host biological processes to achieve a desired outcome [1,2]. In muscle tissue engineering, the use of human mesenchymal stem cells (hMSCs) has been extensively documented due to their excellent capacity for self-renewal and relatively privileged immune compatibility [3].…”

Controlled two-photon photodegradation of PEG hydrogels to study and manipulate subcellular interactions on soft materials

“…7, 8 These results illustrate that a myriad of epigenetic factors, beyond soluble media additives, contribute to the control of cell function. 9, 10 In particular, the extracellular matrix (ECM) serves as a major regulator of cell phenotype 11 by presenting mechanical cues and interacting with the cell through integrin binding. 12, 13 Mechanotransduction relays these physical signals via dynamic focal adhesion formation and cytoskeletal organization, which regulate cell morphology, proliferation, migration, differentiation, and apoptosis via changes in gene expression.…”