Figure 9.

Schematic model summarizing the cell phenotype of human MSC deficient for integrin α2 or α11. Integrins are heterodimeric receptors (white and blue forms) having central roles in establishment of cell to extracellular matrix interactions (e.g., collagen type I, pink shape) and in regulation of crucial cell processes (arrows) by engaging various integrin-, membrane-, actin- and signaling-associated proteins (multi-color dots). As the amount of α-subunit determines the amount of receptor present on the plasmalemma, we applied here a lentiviral delivery of α-subunit-specific shRNA in hMSC. Thereby, highly efficient and stable KD of integrin α1, α2 and α11 was achieved (represented by the translucent α-subunit). Our functional analyses showed that only the deficiency of α2 or α11 integrin leads to significant changes in hMSC behavior on collagen I (red arrows). Most importantly, hMSC maintenance was affected as these cells displayed features typical for cell apoptosis. Taken together, this study reports for the first time that disturbance of collagen I–integrin interactions results in the cell death of MSCs. The image is adapted from Docheva et al.⁷