| Popis: |
In mammals, the placenta plays critical roles in proper embryo development, and in maintaining the health of both the embryo and the fetus. In humans, the defective formation of the placenta is associated with pregnancy disorders such as miscarriage, preeclampsia, and fetal growth restriction. These disorders affect a third of human pregnancies and are almost unique to the human species. Notwithstanding, most of our understanding of human placental development is still based on knowledge from animal studies. But the wide variability in placental development and physiology across the mammalian kingdom makes it difficult to directly translate knowledge from animal studies to the human case. Therefore, there is an urgent need to model the placenta using human cells to accelerate research into human placental development as well as associated disorders. Inducing trophoblast differentiation in human pluripotent stem cells, which possess the ability to differentiate into any cell type, provides a viable alternative to mimicking placental development. In this chapter, we explore novel cell culture modulation approaches being developed to induce human-induced pluripotent stem cells (hiPSCs) to differentiate into trophoblast-like cells. hiPSCs are a preferred cell source because, unlike embryonic stem cells (ESCs), they are free from ethical concerns, and autologous hiPSCs do not suffer from immune rejection. Here, we outline advances in the design and implementation of adhesion restricting culture platforms, namely, the micromesh culture technique and the limited-area culture technique, and demonstrate their applications to directing hiPSCs to differentiate into trophoblast-like lineage cells even in the absence of biochemical stimulation. Overall, the biophysical approaches to induction of trophoblast differentiation from hiPSCs demonstrated here, when fully developed, hold great potential in mimicking placental development in vitro, with important implifications for research into placenta-related pregnancy disorders in humans. Keywords: Cell adhesion; iPS cells; Micromesh culture; Placenta; Self-organization; Trophoblast differentiation; Trophoblast stem cells. |
