A new method of cell engineering has allowed scientists to develop a fully human version of an organ resembling ovaries right in the lab—complete with the ability to develop follicles (fluid-filled ovarian sacs that house developing, unfertilized eggs) and secrete the sex hormone estradiol. This ovarian model, part of an emerging class of miniature organ-like models called “organoids,” could one day be used to study ovarian diseases like cancer and even improve treatments for infertility.
The research was led by the lab of controversial Harvard biologist George Church in collaboration with Gameto, a biotech company that works on female reproduction and has licensed the new ovarian organoid technology for preclinical testing. A paper detailing the results from the team’s ovarian organoid was published on Feb. 21 in the journal eLife.
“Half of the human population is female, and yet historically women’s health has not received anywhere near the attention or funding that is given to conditions that affect men,” Donald Ingber, the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, said in a press release. Ingber, who was not directly involved in the research, added that he is “very excited to see this important step forward in being able to study human ovaries in the lab, and look forward to the insights that such a model will provide about female reproductive health and disease.”
Organoids are not a new concept by any means, but more and more biotechnology groups are jumping on the organoid bandwagon since they provide a way to study in great detail how a healthy or diseased organ develops in the human body. Organoids also offer researchers the opportunity to experiment with different kinds of drugs or treatments under true-to-life conditions. Since induced-pluripotent stem cells (from adult human tissue) are often used nowadays rather than embryonic stem cells, researchers are able to avoid the ethical and political debate over research using human embryos. Even so, certain ethical considerations over the development of brain organoids and human-animal chimeric organoids remain.
Still, organoid research shows no sign of slowing down, in part because of how much better we’re getting at developing these bite-sized clusters of cells and tissue. To make cells in the lab organize into an organoid, scientists give human skin and blood cells a protein concoction that reverts them to an embryonic-like state. From there, they can grow the cells into more specialized types that make up the organs they are designed to model.
Ovarian organoids made in this way typically rely on a mix of human and mouse cells—scientists only use the human cells to make germ cells, which go on to grow into eggs. Cells from mice recapitulate somatic cells in their organoid that would support germ cells in a real-life ovary.
In the new study, the researchers added even more proteins to a subset of human cells so that they would mimic the development of a somatic cell. Not only was their model entirely derived from human cells, it also showed marked benefits compared to previous ovarian organoids. The new organoids produced DAZL, a protein associated with ovary maturation, in just four days—a process that took hybrid human-mouse ovarian organoids 32 days. And after 16 days of growth, the new fully human organoids began to form complex structures reminiscent of follicles.
“The fact that this can be done within five days instead of the month required with human/mouse hybrid ovaroids will dramatically speed up the discovery of critical information about women’s health and reproduction,” Church said in the press release. The ability to study real-time progression of a disease or issue in an organ could help scientists unpack new ways of treating such problems early, or preventing their onset outright.
Gameto’s website lists a preclinical-stage project called Fertilo that will use the technique to improve the results of in-vitro fertilization (IVF). Eventually, with Fertilo, oocytes—the precursors to eggs—would be extracted from a woman and cultured for 24 hours in an ovarian organoid until they are ready for fertilization. This technique, according to Gameto’s website, would reduce the cost of IVF and allow patients to undergo fewer days of hormone shots typically required for the procedure. For the 11 percent of American women who’ve reported experiencing fertility problems, this could potentially make IVF a much more appealing and accessible solution.