The amniotic membrane (AM) forms the inner layer of placenta surrounding a fetus during pregnancy, allowing successful embryonic implantation, providing protection against physical trauma, maintenance of constant temperature, and amniotic fluid flow that assists in musculoskeletal development. Failure of the embryo to implant contributes to loss of pregnancy, which occurs at a rate of 10-12% in the first trimester, as well as to failed in vitro fertilization (IVF), which currently has reported success rates as low as 25%. Growth of functional AM tissue in vitro has not yet been achieved, limiting studies of early human embryonic development and causes of implantation failure due to lack of accessibility to live tissues. Human pluripotent stem cells (hPSCs) are a promising cell source for the formation of amnion-like tissues. While 2D culture of hPSCs can initiate the formation of separate regions that appear to be similar to those formed during the early phase of embryonic development, this type of regionalization is not the same as that of the patterning that occurs in actual embryos.
Development of amnion-like tissue from human pluripotent stem cells
An engineered three dimensional (3D) biomimetic peri-implantation niche can be used to develop self-organized, amnion-like tissues from hPSCs in vitro. The developed technology uses a 3D scaffold composed of a natural biological hydrogel or a microfabricated artificial matrix that mimics physicochemical cues found within the peri-implantation environment, allowing for amniotic tissue morphogenesis by supporting hPSC differentiation and self-organization. The resulting tissue expresses AM-specific molecular marker genes (i.e. periostin) and placental tissue markers (i.e. GATA2/3), with transcriptional similarity to human amnion cells and luminal cyst invasion into the 3D matrix that is consistent with that typically observed in vivo with the invasive amnioblast phenotype. This technology has potential for facilitating the study of early human embryonic development, as well as the use of formed tissues for drug screening applications and therapeutic treatments for failure of embryonic implantation.
- Drug screening
- Study of human embryonic tissue development
- Study of embryonic implantation failure (i.e. early human pregnancy loss)
- Use for understanding of high in vitro fertilization failure rates
- Efficient derivation of human amnion-like tissues