The nesting cell: A stem cell is exposed to multivariate cues including cell-cell interactions, cell-ECM interaction, soluble factors and biophysical factors like substratum rigidity, topography, shear stress, oxygen, and pH (A); Novel techniques like microfluidics, and micro-nanoengineering can allow mimicking the microenvironmental condition a cell experiences in vivo, and allow more precisely control of experimental parameters like shear stress, biochemical gradients, substrate rigidity and nanotopography, and cell positioning (B).