Downregulation of vimentin intermediate filaments affect human mesenchymal stem cell adhesion and formation of cellular projections

Abstract

Mesenchymal stem cells hold great promise as a therapeutic cell source for a variety of diseases such as osteoarthritis and degenerative disc disease. Their unique homing ability and multipotentiality play key roles in their applications in medicine. Specifically, hMSCs capability to adhere and migrate to damaged tissue's extracellular matrix is essential for serving their therapeutic purpose. The roles of some cytoskeletal elements, such as actin and microtubules, in cell migration and adhesion have been well described, while that of intermediate filaments (IFs) is not well understood. There is increasing evidence that vimentin IFs also function in cell spreading and adhesion, but their relationships in MSCs have not been fully characterized. In this work, we sought to understand how vimentin IFs govern adhesion and cellular cytoplasmic projection formation in human MSCs. Using shRNA to knockdown vimentin IFs in MSCs, we found that vimentin IFs are necessary for the cellular structural integrity required for cell-substrate adhesion and for forming and maintaining cellular projections.