Tissue-Engineered Uterus Supports Normal Pregnancy, Live Birth in Rabbits

By Will Boggs MD

July 29, 2020

NEW YORK (Reuters Health) - A tissue-engineered uterus constructed from autologous cells supports normal pregnancy and live birth in a rabbit model, researchers report.

"We know that uterine tissue undergoes major changes, not just for embryo attachment, but also for the entire pregnancy process," Dr. Anthony Atala of Wake Forest University School of Medicine, in Winston-Salem, North Carolina, told Reuters Health by email. "What we found most interesting about the work is that the engineered uterine tissue showed the expected changes with pregnancy over time, similar to those observed in normal uterine tissue."

Allogeneic uterine transplantation is a promising treatment for uterine infertility, but it requires donors and the use of antirejection therapies. Creating a uterus from a woman's own cells combined with biomaterials requires no donor and minimizes the risk of immunological rejection.

Dr. Atala and colleagues used biodegradable polymer scaffolds seeded with rabbit primary uterine-derived cells to generate uterine constructs, which they then implanted into rabbits. Control rabbits received a nonseeded scaffold or had the excised defect repaired by suturing the remaining edges.

Serial hysterograms at six months showed that the tissue-engineered group had patent uterine cavities with a preserved uterine configuration, whereas the nonseeded scaffold group had multiple filling defects and marked strictures along the lumen. The subtotal excision-only controls had severe proximal luminal blockage and incomplete contrast filling of the cavity.

Three months after surgery, the scaffold material had completely biodegraded. The tissue-engineered group uteri had developed an epithelial lining, distinct stroma with glandular structures, and smooth-muscle bundles in the outer layer, whereas the nonseeded group had partially formed stromal layer, scarce smooth-muscle fibers and greater collagen content.

Among 42 rabbits used in pregnancy studies, four of 10 rabbits receiving the tissue-engineered constructs had normal pregnancies resulting in live births of average weight with no congenital malformations, the researchers report in Nature Biotechnology.

Macroscopically, there were no defects or herniation along the pregnant engineered uterus, and histological analyses confirmed normal uterine tissue structures and placental development.

None of the rabbits that received nonseeded scaffold constructs or that underwent subtotal excision alone had fetal development or placentation at the reconstructed segment of the uterine horn.

"Engineered uterine tissue can promote fertility, pregnancy, and fetal development to term with normal offspring," Dr. Atala said. "Because the strategy is designed to use the patients' own cells, clinically there would be no rejection and, therefore, no need for antirejection medications."

"We are doing all the needed work required to show that the technology can be effective in larger models and can be safe long term," he said.

SOURCE: https://go.nature.com/3ivnfQb Nature Biotechnology, online June 29, 2020.

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