Scientists at Women & Infants Hospital and Brown University, Rhode Island have invented the first artificial human ovary, providing a possible new method for carrying out fertility research, as well as potential infertility treatments for patients with cancer. The researchers say they have already used the lab-grown organ to mature human eggs. This innovation has been published in the Journal of Assisted Reproduction and Genetics
Sandra Carson, professor of obstetrics and gynecology, the Warren Alpert Medical School of Brown University and director of the Division of Reproductive Endocrinology and Infertility at Women & Infants Hospital, and senior author, said:
An ovary is composed of three main cell types, and this is the first time that anyone has created a 3-D tissue structure with triple cell line.
The scientists say that the artificial ovary provides a living laboratory for researching fundamental questions regarding the functions of healthy ovaries, as well as being a test bed to determine how problems, such as chemical or other toxins can undermine egg health and maturation.
This innovation might eventually help patients facing cancer treatment preserve fertility, wrote lead author Stephan Krotz, a fertility specialist from Houston, Texas. Before chemotherapy or radiation therapy the patient's immature eggs could be salvaged and frozen, and then matured outside the patient in the artificial ovary.
Jeffrey Morgan, associate professor of medical science and engineering, invented the means for bringing all three ovarian cell types into a 3-D arrangement similar to a real ovary in the body, making the artificial ovary a functional tissue and not just a cell culture. His so-called 3D Petri dishes are made of a moldable agarose gel that provides a nurturing template to encourage cells to assemble into specific shapes.
The scientists formed honeycombs of theca cells, one of the main types in the ovary, which were donated by patients aged between 25 and 46. The theca cells grew into the honeycomb shape, and then spherical clumps of donated granulosa cells were placed into the honeycomb holes together with oocytes (human egg cells). After a couple of days the theca cells enveloped the granulosa and eggs, as would occur in a real ovary.
They then had to determine whether the structure could mature eggs, like a real ovary does. In experiments the structure nurtured eggs from the "early antral follicle" stage to full maturity.
The authors wrote:
[This] represents the first success in using 3-D tissue engineering principles for in vitro oocyte maturation," the researchers wrote in the journal article.
Sandra Carson said her aim was to create a research environment where she could study how theca and granuloso cells and oocytes interact, rather than to invent an artificial organ. When Morgan told her about the 3-D Petri dishes, the started to collaborate on creating an organ. This is the first fully functional tossie to be made using the method, Morgan said.
Carson and Morgan say they continue collaborating and are now commencing new studies.
The authors concluded:
An artifical human ovary can be created with self-assembled human theca and granulosa cell microtissues, and used for IVM and future oocyte toxicology studies.
"In vitro maturation of oocytes via the pre-fabricated self-assembled artificial human ovary"
Stephan P. Krotz, Jared C. Robins, Toni-Marie Ferruccio, Richard Moore, Margaret M. Steinhoff, Jeffrey R. Morgan and Sandra Carson
Journal of Assisted Reproduction and Genetics
Written by Christian Nordqvist