Artificial ovary uses cells to deliver hormone replacement therapy

Women whose ovaries stop functioning because of either menopause or disease can experience health effects that go beyond the loss of fertility, including osteoporosis and obesity. The standard treatment—hormone replacement with estrogen alone or in combination with progestin—can mitigate those problems. But the treatment comes with other risks, including an increased chance of breast cancer and heart disease. A team led by Emmanuel C. Opara of Wake Forest School of Medicine is developing bioengineered polymeric capsules that mimic ovarian follicles for use as a cell-based method of hormone replacement (Nat. Commun. 2017, DOI: 10.1038/s41467-017-01851-3). To make these artificial ovaries, the researchers encapsulate two types of hormone-producing ovarian cells—granulosa and theca cells—in separate layers of cross-linked alginate (a polysaccharide) with layers of poly-l-ornithine between. They tested the capsules by implanting them in rats whose ovaries had been removed and comparing the performance with rats whose ovaries had been removed and treated using hormone-containing pellets at high and low doses of estrogen with or without progestin. After 90 days, rats that received the cell-based therapy had similar body weight, fat percentage, bone mineral density, and uterine morphology as rats with intact ovaries. These positive effects were achieved with hormone levels in the blood that were lower in rats receiving the cell-based therapy than in rats receiving the hormone pellets or in rats whose ovaries were still intact.