Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation
- 21 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Biomechanics and Modeling in Mechanobiology
- Vol. 10 (6), 939-953
- https://doi.org/10.1007/s10237-010-0285-8
Abstract
Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle (SMCs) and endothelial cells (ECs). This was tested using a unique experimental platform to differentially apply various mechanical stimuli in parallel. Three forces, cyclic stretch, cyclic pressure, and laminar shear stress, were applied independently to mimic several vascular physiologic conditions. Experiments were conducted using subconfluent MSCs for 5 days and demonstrated significant effects on morphology and proliferation depending upon the type, magnitude, frequency, and duration of applied stimulation. We have defined thresholds of cyclic stretch that potentiate SMC protein expression, but did not find EC protein expression under any condition tested. However, a second set of experiments performed at confluence and aimed to elicit the temporal gene expression response of a select magnitude of each stimulus revealed that EC gene expression can be increased with cyclic pressure and shear stress in a cell-contact-dependent manner. Further, these MSCs also appear to express genes from multiple lineages simultaneously which may warrant further investigation into post-transcriptional mechanisms for controlling protein expression. To our knowledge, this is the first systematic examination of the effects of mechanical stimulation on MSCs and has implications for the understanding of stem cell biology, as well as potential bioreactor designs for tissue engineering and cell therapy applications.Keywords
This publication has 85 references indexed in Scilit:
- Mechanical regulation of cell function with geometrically modulated elastomeric substratesNature Methods, 2010
- Cytokine-Induced Signaling Networks Prioritize Dynamic Range over Signal StrengthCell, 2008
- Global Changes in Optic Nerve Head Gene Expression after Exposure to Elevated Intraocular Pressure in a Rat Glaucoma ModelInvestigative Ophthalmology & Visual Science, 2007
- Cyclic Pressure Stimulates DNA Synthesis through the PI3K/Akt Signaling Pathway in Rat Bladder Smooth Muscle CellsAnnals of Biomedical Engineering, 2007
- Anisotropic mechanosensing by mesenchymal stem cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- A New Experimental System for the Extended Application of Cyclic Hydrostatic Pressure to Cell CultureJournal of Biomechanical Engineering, 2006
- Cyclic hydrostatic compression stimulates chondroinduction of C3H/10T1/2 cellsBiomechanics and Modeling in Mechanobiology, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Frequency- and Duration-Dependent Effects of Cyclic Pressure on Select Bone Cell FunctionsTissue Engineering, 2001
- Effect of pressure on cultured smooth muscle cellsLife Sciences, 1997