Research press release


Nature Communications

Biotechnology: Cell-based hormone replacement therapy works in rats



今回、Emmanuel Oparaたちの研究グループは、生物工学的に作製された3D卵巣構築物に2種類の卵巣細胞(顆粒膜細胞と莢膜細胞)を封入し、卵巣を摘出されたラットに移植した。90日の研究期間中、移植された卵巣構築物は、自然に起こる細胞間相互作用を再現し、低濃度のホルモン(主にエストロゲンとプロゲステロン)を安定的に産生した。この卵巣構築物は、ホルモン欠乏状態や卵巣の喪失に通常伴う副作用(骨密度、体重又は子宮の健康状態の変化)を緩和することも明らかになった。


An alternative option to pharmacological hormone replacement therapy (pHRT) is reported in a rodent study in Nature Communications. Cell-based hormone replacement therapy, which uses a 3D bioengineered ovary construct to deliver and regulate sex hormones, is shown to be as effective as pHRT, but with fewer adverse side effects.

Hormone replacement therapy is not just for women at the age of menopause but also for cancer patients who undergo treatment affecting their ovaries. Different treatment approaches are needed, as the adverse effects of higher levels of hormones associated with pHRT are currently deemed to outweigh its benefits. Cell therapies have been proposed as an alternative treatment option as they can provide additional benefits beyond drug treatment: namely, that cells can secrete more than one hormone at a physiological level, and the cells can signal to the brain, thereby mimicking the role of fully functional ovaries.

Emmanuel Opara and colleagues encapsulate two ovarian cell types (granulosa and theca cells) in a 3D bioengineered ovary construct and transplant them into rats whose ovaries have been removed. On implantation, the ovarian constructs recapitulate native cell-cell interactions and produce hormones (primarily oestrogen and progesterone) at low levels stably for the 90 days studied. These constructs are shown to ameliorate adverse effects normally associated with hormone deficiency or loss of an ovary, such as changes in bone density, body weight or uterine health.

This is a proof-of-concept paper that shows that such cell-based therapy with 3D bioengineered ovarian constructs could act to mimic the organ, producing low but sufficient levels of hormones, in a rat model. As this study was conducted in animals, extensive additional work will be needed before possible application to the clinic.

doi: 10.1038/s41467-017-01851-3

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