Ever since they were first isolated, amnion-based stem cells have been considered promising candidates for cell therapies because of their ease of access, plasticity, and absence of ethical issues in their derivation and use. However, a Japanese research team has discovered that stem cells derived from human female amnion also have the ability to suppress the inappropriate activation of the immune system and that there are straight-forward ways to enhance their immunosuppressive potential.
The amniotic membrane is a three-layered structure that surrounds the baby and suspends it in amniotic fluid. Amniotic fluid acts as a protective shock-absorber, a lubricant and an important physiological player in the life of the embryo and fetus. Because the fetus is a privileged entity that escapes attack from the mother’s immune system, researchers have been very interested in determining the immunological properties of the amnion cells.
“The human amniotic membrane contains both epithelial cells and mesenchymal cells,” said study co-author Dr. Toshio Nikaido, Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences at the University of Toyama. “Both kinds of cells have proliferation and differentiation characteristics, making the amniotic membrane a promising and attractive source for amnion-derived cells for transplantation in regenerative medicine. It is clear that these cells have promise, although the mechanism of their immune modulation remains to be elucidated.”
In this study by Nikaido and his coworkers, amnion-derived cells inhibited natural killer cell activity and induced white blood cell activation. Nikaido reported that he and his colleagues saw the amnion-derived cells increase production of a molecule called interleukin-10 (IL-10).
“We consider that IL-10 was involved in the function of amnion-derived cells toward NK cells,” explained Dr. Nikaido. “The immunomodulation of amnion-derived cells is a complicated procedure involving many factors, among which IL-10 and prostaglandin E2 (PGE2) play important roles.”
Molecules called “prostaglandins,” such as PGE2, mediate inflammation, smooth muscle activity, blood flow, and many other physiological process. In particular, PGE2 exerts important effects during labor and stimulates osteoblasts (bone-making cells) to release factors that stimulate bone resorption by osteoclasts. PGE2 also suppresses T cell receptor signaling and may play a role in the resolution of inflammation.
When Nikaido and others used antibodies against PGE2 and IL-10, they removed the immunosuppressive effects of the amnion-derived cells on natural killer cells. These data imply that these two factors contribute to the immunosuppressive abilities of amnion-derived cells.
“Soluble factors IL-10 and PGE2 produced by amnion-derived cells may suppress allogenic, or ‘other’ related immune responses,” concluded Dr. Nikaido. “Our findings support the hypothesis that these cells have potential therapeutic use. However, further study is needed to identify the detailed mechanisms responsible for their immodulatory effects. Amnion-derived cells must be transplanted into mouse models for further in vivo analysis of their immunosuppressive activity or anti-inflammatory effects.”
Given the levels of autoimmune diseases on the developed world, these results could be good news for patients who suffer from diseases like Crohn’s disease, systemic lupus erythematosus, or rheumatoid arthritis. While more work is needed, amnion-based cells certainly show promise as immunosuppressive agents.
The study will be published in a future issue of Cell Transplantation.