The female uterus is essential for reproduction in all mammals, meaning any trauma or disease affecting this organ detrimentally could compromise a woman’s ability to conceive or carry a viable fetus to term. The transplant of donor uteri has demonstrated potential in the reversal of infertility caused by a dysfunctional uterus even though it requires the use of anti-rejection therapeutics.
There has also been much interest surrounding bioengineered uteri using biodegradable scaffolding seeded with the patient’s own cells. This is desirable as it avoids the risk of disease or the need for antirejection drugs accompanying the transplant of donor organs.
The use of this regenerative technique has previously been trialed in humans resulting in the successful implantation of bioengineered bladders, blood vessels, urethras, and vaginas in human patients.
Now, a study from researchers at the Wake Forest Institute for Regenerative Medicine (WFIRM) bioengineer uteri capable of supporting fertilization, fetal development, and live birth in rabbits. The team states this approach may someday provide a solution for women faced with the inability to get pregnant due to an irregular uterus. The opensource study is published in the journal Nature Biotechnology.
Rebuilding an infertile uterus
Previous studies have indicated the regeneration of uteri is only successful where small defects are involved, making translation to larger animals and humans unfeasible.
In multiple rodent studies, small defects in uteri were successfully repaired using an assortment of constituents such as non-degradable synthetic polymer scaffolds, biodegradable synthetic polymer scaffolds, naturally derived scaffolds, and scar tissue.
Despite this, attempts at regenerating larger uterine defects using these strategies have failed. The current study bioengineers uteri with large defects in rabbits that went on to develop normal, native structures and restore normal reproductive function.
The current study observes rabbits who had undergone a subtotal uterine excision and were reconstructed using either a scaffold seeded with the animals’ own cells or unseeded polymer scaffolds or by suturing only. A normal control group was also part of the study group.
The biodegradable polymer scaffolds were 6–8 cm in length, and 2.5 cm in width, composed of poly-dl-lactide-coglycolide (PLGA)-coated polyglycolic acid (PGA) seeded with the rabbit’s personal uterine cells.
Live births with engineered uteri
Six months after the cell-seeded and unseeded scaffolds were implanted, the female rabbits were mated with fertile male rabbits. Results show after this period of time only the cell-seeded uteri developed natural structures, such as stroma, luminal/glandular epithelium, vascularized mucosa, and two-layered myometrium. Data findings show only rabbits possessing cell-seeded engineered uteri were able to support a normal pregnancy, with forty percent of this group capable of supporting regular fetal development to term and live birth.
The lab states their cell-seeded constructs supported tissue expansion at more than ten times its own weight and reconstruction during pregnancy to accommodate the growing fetus, placenta, and amniotic fluid.
They go on to add the resultant offspring’s body weights were similar to those of the normal controls, suggesting normal placental function. They conclude although the number of fetuses per pregnancy was lower than in the normal controls, the engineered uteri supported fetal development and pregnancies to term with live births in four out of fourteen cases.
Engineered uteri in human trials
The team surmises their regenerative technique used to create uterine tissue is able to support normal pregnancies and fetal development comparable to those produced in a normal uterus. For the future, the researchers state this approach may provide a pathway to pregnancy for women with a defective uterus, however, further preclinical studies must be carried out before clinical trials are designed.
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