Mice whose ovaries were removed and replaced with an artificial structure were able to have offspring naturally, scientists have revealed in a breakthrough that could lead to the “holy grail of bioengineering” in humans.
The ovary structure was 3D-printed using gelatin to create a lattice that could house follicles containing the eggs.
The researchers said the new technique could one day be used to restore fertility to women rendered infertile by cancer treatment.
And they also suggested it could also help design a range of artificial organs that could be used instead of transplants from dead people, which require the patient to take immune-suppressing drugs for the rest of their lives.
One of the researchers, Professor Teresa Woodruff, of Northwestern University in the US, said: “Using bioengineering, instead of transplanting from a cadaver, to create organ structures that function and restore the health of that tissue for that person, is the holy grail of bioengineering for regenerative medicine.
“The exciting part of this new discovery is that we are going to be able to build ovaries that we hope one day will help restore fertility to young cancer survivors as well as children going through puberty who have been treated with life-preserving cancer treatments but are going to be sterilised by that same treatment.
“We have never had a way to provide back that fertility. We can protect their fertility but we’ve not been able to restore it.
“What that means is they are going to have endocrine function – endocrine hormones like oestrogen and progesterone – and they are going to have the ability to have their own children one day.
“That’s the real promise of this technology.”
She said the prosthetic ovaries had been showed to have a “long-term, durable function”.
Crucially, the mice with the prosthetic ovaries produced milk in the normal way as a result of the normal hormonal changes in their body.
A paper in the journal Nature Communications said ovarian function had been “fully restored … in surgically sterilized mice”.
“The techniques developed here are the necessary first steps to validate the significant undertaking of exploring such an approach for creating a human bioprosthetic ovary,” the paper added.
“Live birth was achieved with the implant alone; angiogenic growth factors [used to encourage new blood vessels], hormone stimulation and embryo transfer were not required.
“The resulting pups from the bioprosthetic ovary developed normally with their own reproductive competency, as they were all able to sire or deliver healthy litters.”
However the researchers cautioned that further work was required to establish whether the synthetic ovary would function in the same way in humans and that there was not a risk of cancerous cells.
“This bioprosthetic ovary may become a promising solution for restoring hormone and fertility function in oncofertility [cancer] patients,” the paper said.
“Outside of reproductive biology, our findings will likely impact others developing tissue units … and underscore the importance of independently investigating the impact of architectural variables when designing scaffolds for other soft tissue and organ targets.”
Gelatin is a hydrogel made from collagen, which is found in human’s bones and skin and is safe to use inside the body.
Professor Ramille Shah, an expert in materials science at Northwestern, said: “Most hydrogels are very weak, since they're made up of mostly water, and will often collapse on themselves.
“But we found a gelatin temperature that allows it to be self-supporting, not collapse, and lead to building multiple layers. No one else has been able to print gelatin with such well-defined and self-supported geometry.”
She added that the study was also the first to show that the “scaffold architecture makes a difference” in the survival of ovarian follicles, which each contain a single egg.
In some cancer patients, the ovaries do not function at a high enough level and hormone replacement therapy is required.
Dr Jane Stewart, the chair-elect of the British Fertility Society, said the paper “sounds really exciting”.
“They have managed to create a matrix in which they can embed ovarian tissue and they’ve then managed to implant that back in a mouse and made it work,” she said.
“From a human point of view we are way off being able to use that in clinical practice, but it’s a step towards that.”
Dr Stewart said this technique still required the existence of ovarian follicles containing eggs.
But other researchers are working on ways to produce these from stem cells, which could eventually allow the artificial construction of a complete ovary with eggs genetically related to the woman.
She said ovarian tissue was currently removed from cancer patients and then grafted back to allow them to have children.
But eggs were lost during the process and the artificial ovarian structure might help reduce this, allowing the women to have children naturally, rather than requiring IVF.
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