Control of stem cell fate and function by engineering physical microenvironments

Abstract

The phenotypic expression and function of stem cells are regulated by their integrated response to variable microenvironmental cues, including growth factors and cytokines, matrix-mediated signals, and cell-cell interactions. Recently, growing evidence suggests that matrix-mediated signals include mechanical stimuli such as strain, shear stress, substrate rigidity and topography, and these stimuli have a more profound impact on stem cell phenotypes than had previously been recognized, e.g. self-renewal and differentiation through the control of gene transcription and signaling pathways. Using a variety of cell culture models enabled by micro and nanoscale technologies, we are beginning to systematically and quantitatively investigate the integrated response of cells to combinations of relevant mechanobiological stimuli. This paper reviews recent advances in engineering physical stimuli for stem cell mechanobiology and discusses how micro-and nanoscale engineered platforms can be used to control stem cell niche environments and regulate stem cell fate and function.

In situ tissue engineering with synthetic self-assembling peptide nanofiber scaffolds, PuraMatrix, for mucosal regeneration in the rat middle-ear

“…65 On the other hand, peptide hydrogels are mechanically weak, and this feature is disadvantageous for tissue engineering, 15 because adherent tissue cells must, in general, attach to a solid substrate for their survival, and mechanical stiffness of scaffold materials for tissue engineering is important for cell proliferation. 63,66,67 However, one previous study indicated that adhesion and proliferation of human umbilical vein endothelial cells for 5 days was higher in PuraMatrix (0.275% w/v) than PEG (7.84% w/v), although the elastic and viscous moduli of PuraMatrix were lower than those of PEG. 68 Taken together, the results indicate a better engraftment rate with the use of low cell density compared with high cell density.…”

Topography Design Concept of a Tissue Engineering Scaffold for Controlling Cell Function and Fate Through Actin Cytoskeletal Modulation

“…135 At the same time, a growing number of researchers have recognized the significant role of the ECM niche in a tissue where stem cells reside. 111,[136][137][138][139] The effect of actin cytoskeletal tension on commitment to a stem cell lineage has been best characterized for MSCs in many studies, 140 including those using the high-content image-based approach for the prediction of a lineage fate of stem cells. 141,142 As summarized in Table 1, osteogenic lineage commitment and inhibition of differentiation into other lineage types require actin cytoskeletal tension mediated by RhoA and ROCK in human, 61,106,[143][144][145] mouse, 146 and rat 132 MSCs.…”

Enhanced Directional Migration of Cancer Stem Cells in 3D Aligned Collagen Matrices

“…This population is highly plastic with bidirectional interconversions between stem and nonstem (i.e., more differentiated) states (24,25) and is known to possess robust tumor-sustaining properties, drug resistance, and increased metastatic potency (21,22,26). Further, the physical properties of the cell microenvironment, including stiffness and topology, have been demonstrated to influence (noncancerous) stem cell behavior (27). Thus we postulated that CSCs may respond more robustly to the biophysical features of the tumor ECM that promote disease progression such as aligned collagen.…”