Figure 8.

Spatiotemporal concentration profiles of autocrine and paracrine factors and their effect on the cell phenotype. (A) LIF activates STAT3 and induces self-renewal. In this study, the effects of the flow rate, the position of the flow field and the local field organization on STAT3 activation and the fate of mESC were analyzed, mathematically described, and compared with the static culture. (B and C) Effect of endogenous autocrine and paracrine factors on stem cell differentiation of mESC. (B) In a flow chamber, Nanog, Klf4, and Rex1 were washed off from stem cells, which induces differentiation. (C) Adding endogenous factors to the medium (complex medium, CM) allows the impact of each of these factors on stem cell self-renewal and maintenance of the undifferentiated stage to be studied. (D) Stable TNFα gradient across a rectangular diffusion chamber. Across the chamber, there is a minimal flow that does not disturb the spatiotemporal gradients of secreted molecules from the cells. Sink and drain channels perpendicular to the chamber maintain the gradient constant, which allows global effects of TNFα on cells to be studied without disrupting the local cell–cell pattern. (A and B) Adapted with permission from refs (67 and 110). Copyright 2012 Proceedings of the National Academy of Sciences. (C) Adapted with permission from ref (111). Copyright 2011 Public Library of Science. (D) Adapted with permission from ref (112). Copyright 2013 Royal Society of Chemistry.