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The transplantation of stem cells for use in regenerative medicine, where diseased or degenerated tissue is replaced with a new cell source, is an exciting field of research. However, prior to the implementation of a cell therapy, large amounts of cells will be required, and a consistent protocol for the development of functional cells, in large homogeneous populations must be developed for each cell type of interest.  

Endothelial cells have potential for use in cardiovascular applications, such as promoting vascularisation within the host tissue near an implanted tissue engineered product. Endothelial cells have been previously differentiated from embryonic stem cells; one common differentiation method is to culture the cells in a medium containing growth factors relevant to endothelial lineage differentiation. However, this method results in a low efficiency of endothelial differentiation.

In vivo, endothelial cells line the surface of blood vessels. They regularly experience a fluid shear stress due to the constant fluid movement of blood through the circulatory system.  By applying a shear stress to murine embryonic stem cells in vitro, at levels similar to those experienced by endothelial cells in vivo, researchers were able to obtain a much higher yield of differentiation; 1% of cells differentiated without shear stress, while 40% of cells differentiated with the application of constant shear stress. Other studies have also looked at endothelial cell differentiation with respect to shear stress, from initial cell populations of bone marrow mesenchymal stem cells, and adipose-derived stem cells, where shear stress was also found to increase endothelial differentiation.

These significant increases in differentiation yields are important with respect to both the potential use of endothelial cells in regenerative medicine, as well as in other stem cell fields. While recreating the in vivo environment is not a new approach, it is shown to be a very effective strategy with regards to enhancing differentiation. The in vivo environment may be something that other researchers should consider in when developing differentiation protocols for stem cells.

Future research considerations may include applying this technique to human cells and the purification of the resulting cell population, so that transplanted cells perform only the desired function.

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Allison Van Winkle

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