A fully human ovarian organoid has been grown in the lab for the first time, with potential applications to improve understanding and treatment of female infertility.
Ovarian development – in the body or in vitro – requires both germ cells and somatic cells. Previous ovarian organoids used a combination of human germ cells and mouse somatic cells, but the new 'ovaroids' developed by scientists at the Wyss Institute at Harvard, Massachusetts, used human stem cells. The ovaroids demonstrated key ovarian functions, including hormone signalling, supporting the maturation of germ cells, and follicle formation but did not produce eggs.
'Our new method of fully human ovaroid production … replicates many of the critical functions of these organs, marking a significant step forward in our ability to study female reproductive health in the lab' said co-first author Merrick Pierson Smela, a graduate student at Harvard Medical School.
The research, published in eLife, was a collaboration with the biotechnology company Gameto. The team used human induced pluripotent stem cells which were induced to become granulosa-like cells – an ovarian somatic cell type which help eggs grow and mature.
Next, the scientists cultured the granulosa-like cells with human primordial germ cell-like cells, forming the fully human ovaroids.
After four days the new ovaroids started to produce a protein called DAZL which is a marker of germ cell maturation. Follicle-like structures formed after 16 days, however, the germ cells did not live long enough to develop further into egg cells.
'I'm very excited to see this important step forward in being able to study human ovaries in the lab and look forward to the insights that such a model will provide about female reproductive health and disease' said Professor Donald Ingber, founding director of the Wyss Institute.
The authors hope that their model, with further optimisation, may have applications in human in vitro oogenesis: deriving fertilisable oocytes in vitro from stem cells:
'In the future, similar technology could also treat infertility by growing egg cells from people whose own eggs aren't viable,' said Pierson Smela.
Sources and References
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Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression
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Gameto licenses Wyss Institute's technology for growing human ovaries from Harvard University
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Human ovarian organoids to improve women's health
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Fully human ovarian organoid that supports egg cell maturation created by laboratory researchers
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Harvard scientists say they can grow ovaries in a lab
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How a lab-grown ovary can shake up infertility treatment
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