Introduction: Induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have the potential for therapeutic application in several cardiovascular diseases. Mechanical strain is known to regulate EC behavior and stem cell differentiation and may play a role in directing EC differentiation of iPSCs. , a long non-coding RNA (lncRNA), is known to affect ECs in several mechanically relevant pathologies and may play a role in this process as well. Therefore, we investigated expression changes of resulting from mechanical stimulation during EC differentiation, as well as functional effects on EC tube formation.
Methods: iPSCs were subjected to 5% cyclic mechanical strain during EC differentiation. RT-PCR and flow cytometry were used to assess changes in mesoderm differentiation and gene expression in the final ECs as a result of strain. Functional outcomes of mechanically differentiated ECs were assessed with a tube formation assay and changes in . was also overexpressed in human umbilical vein endothelial cells (HUVECs) to assess its role in non--expressing ECs.
Results: Mechanical strain promoted mesoderm differentiation, marked by increased expression of brachyury 24 h after initiation of differentiation. Strain also increased expression of , , VE-cadherin, and in differentiated ECs. Strain-differentiated ECs formed tube networks with higher junction and endpoint density than statically-differentiated ECs. Overexpression of in HUVECs resulted in similar patterns of tube formation.
Conclusions: expression is increased by mechanical strain and promotes tube branching in iPSC-derived ECs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479073 | PMC |
| http://dx.doi.org/10.1007/s12195-020-00617-0 | DOI Listing |
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