Engineering placental trophoblast fusion: A potential role for biomechanics in syncytialization

The process by which placental trophoblasts fuse to form the syncytiotrophoblast around the chorionic villi is not fully understood. Mechanical features of the in vivo and in vitro culture environments have recently emerged as having the potential to influence fusion efficiency, and considering these mechanical cues may ultimately allow predictive control of trophoblast syncytialization. Here, we review recent studies that suggest that biomechanical factors such as shear stress, tissue stiffness, and dimensionally-related stresses affect villous trophoblast fusion efficiency. We then discuss how these stimuli might arise in vivo and how they can be incorporated in cultures to study and enhance villous trophoblast fusion. We believe that this mechanical paradigm will provide novel insight into manipulating the syncytialization process to better engineer improved models, understand disease progression, and ultimately develop novel therapeutic strategies.