Health In Focus
  • In one form of infertility, the implanted embryo fails to grow beyond the initial few days or weeks, leading to pregnancy loss; the reasons remain unclear
  • Novel human stem cell derived amniotic sac structure may help understand key events during early pregnancy, and aid infertility research and treatment

Stem cell derived post-implantation amniotic sac embryoid (PASE), which resembles human amniotic sac, could prove to be of great value in gaining insight into early post-implantation events, and guide future infertility research and treatment, according to a research team at the University of Michigan.

Their work has been published in Nature Communications in August 2017

Importance Of Lab Grown Amniotic Sac - Aim Of Study

Many couples, although they may achieve pregnancy, are unable to go past the initial developmental stage of the embryo. Such couples remain infertile and the key events in the post-implantation period that take the pregnancy forward remain unclear and consequently the reasons for such cases of infertility and little can be done to help such couples.
Boost To Infertility Research – Stem Cell Derived Amniotic Sacs

The research team aimed to probe these little known mysteries surrounding the early development phase of the embryo in the quest of answers and managed to develop a amniotic sac structure from human pluripotent stem cell that grew on a specially engineered surface for the purpose.

This in itself constitutes a remarkable feat and is a first as previous teams have only been able to induce donated embryos to grow. The work of the current team could provide scientists an opportunity to explore unknown frontiers, while avoiding ethical issues associated with studying actual embryos.

"As many as half of all pregnancies end in the first two weeks after fertilization, often before the woman is even aware she is pregnant.For some couples, there is a chronic inability to get past these critical early developmental steps, but we have not previously had a model that would allow us to explore the reasons why," says co-senior author Deborah Gumucio, Ph.D.

The Post-implantation Amniotic Sac Embryoid (PASE)

  • The amniotic sac structure created from pluripotent stem cells was dubbed post-implantation amniotic sac embryoid (PASE). The stem cells spontaneously acquired similar structural and molecular features seen in a natural amniotic sac of pregnancy.
  • The amniotic is an asymmetric, hollow ball-like structure composed of cells that will give rise to a part of the placenta as well as the embryo itself. However, as the structure lacked other crucial components of the embryo, it would not be able to develop into a fetus.
  • The PASE has two distinct halves that remain stable even as cells divide. One half is composed of cells which will be the future amniotic ectoderm, and the other half consists of pluripotent epiblast cells that make up the embryonic disc. The hollow center is similar to the amniotic cavity, from which the amniotic sac is derived, that protects and cushions the fetus as it grows during a normal pregnancy.
Gumucio compares the PASE to a mismatched plastic Easter egg or a blue-and-red Pokémon ball, having two well delineated halves composed of different kinds of cells that remain stable form around a hollow center.
  • The team were also able to study details about the genes that became turned on during the development of a PASE, and the cell signaling that took place between the cells. They reveal that the stable two-halved PASE structure employs a signaling pathway called BMP-SMAD which has been found to be critical during early embryonic development.
  • Interestingly, the PASE structures even showed early signs of formation of a "primitive streak", although it did not develop further. In a normal human embryo, the streak would initiate the phenomenon of gastrulation.
Gastrulation represents the division of the early embryonic cells into three germ layers -- endoderm, mesoderm and ectoderm, from which ultimately, all organs and tissues in the body are derived.

Earlier Research That Led To This Study

The current study follows directly from an earlier collaborative project between Gumucio's lab and that of the other senior author, U-M mechanical engineering associate professor Jianping Fu, Ph.D.
  • In the earlier work, which appeared in Nature Materials, the team managed to make balls of stem cells attach (implant) on to a special surface similar to a simplified uterine wall, engineered in Fu's lab. Once the cells attached themselves to this surface, it was seen that they began to differentiate into hollow spherical cysts consisting entirely of amnion - a tough extraembryonic tissue that holds the amniotic fluid.
  • On further analysis of these cystic structures by co-first authors of the new paper Yue Shao, Ph.D., a graduate student in Fu's lab, and Ken Taniguchi, a postdoctoral fellow in Gumucio's lab, they found that a small proportion of these cysts appeared stably asymmetric and actually resembled early human and monkey amniotic sacs.
  • Also the scientists established that these amniotic sac structures could be formed from induced pluripotent stem cells (iPSCs) i.e human skin cells modified in the lab to acquire the quality of pluripotency or ability to differentiate into any tissue in the body (similar to embryonic stem cells).

 Scope Of This Study And Future Plans

  • Skin cells donated by couples suffering from chronic infertility could be modified into iPSCs and analysed for their ability to form stable amniotic sacs employing the techniques developed by the team.
  • Additional characteristics of the amniotic tissue and the PASE will be delved into in future studies
  • The team plans to identify similarities between human and mouse amniotic tissue since mouse models are an attractive option to study human genetic diseases
In conclusion, this study offers a huge opportunity to understand the early embryonic events better and apply the knowledge in further studies and treatment of infertility.

  1. Yue Shao, Kenichiro Taniguchi, Ryan F. Townshend, Toshio Miki, Deborah L. Gumucio, Jianping Fu. A pluripotent stem cell-based model for post-implantation human amniotic sac development. Nature Communications, (2017); 8 (1) DOI: 10.1038/s41467-017-00236-w
Source: Medindia

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