Cancer reproduction, ovarian freezing, decellularization, artificial ovary

Cancer Reproduction

Ovarian freezing has been applied to preserve the fertility of young women with cancer, and over 180 live births have been achieved after thawing and transplantation worldwide. However, if minimal residual disease (MRD) is present in the frozen ovaries due to cancer metastasis, transplantation may lead to recurrence of the original disease. To avoid recurrence, a method has been considered in which isolated follicles are introduced into a transplantable artificial matrix to create an artificial ovary and then transplanted. Currently, artificial ovaries that mimic natural organs are being developed using artificial materials such as alginate and fibrin. Meanwhile, in recent years, it has been reported that artificial ovaries with MRD removed can be created by decellularizing human ovarian tissue. Unlike conventional gel matrices, this is a matrix derived from a living organism, so it retains factors that promote cell-cell interactions necessary for follicle development. In this study, as a model experiment, mouse follicles are introduced into decellularized human ovarian tissue and transplanted into immunodeficient mice to examine their developmental ability. The research method involves decellularizing human ovarian tissue, isolating interstitial cells from the ovarian tissue at the same time, and isolating follicles from black C57BL/6 mice. Artificial ovary group A was created by introducing black C57BL/6 mouse follicles into decellularized ovaries, while artificial ovary group B was created by introducing human ovarian stromal cells and black C57BL/6 mouse follicles into decellularized ovaries. Either artificial ovary A or artificial ovary B was implanted into white ICR female mice that had had both ovariectomized, and hormone production was confirmed and follicular development was histologically compared between the two groups. These were then mated with white ICR mice to obtain offspring (black mice).

The artificial ovary uses decellularized human ovarian tissue instead of the conventional gel matrix.

Unlike conventional artificial gel matrices, this is a matrix of biological origin, and therefore contains factors that promote the intercellular interactions necessary for follicle development, which is thought to make it easier to produce live births.

Ovarian freezing is used to preserve fertility in young women with cancer, but avoiding recurrence of the original disease due to MRD remains a challenge.
By using the "artificial ovary made from decellularized human ovarian tissue" into which isolated human primordial follicles established in this study are introduced, theoretically there will be no MRD and live births will be obtained without recurrence of the primary disease due to transplantation.

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