Initiation of puberty in mice following decellularized ovary transplant

Abstract

Clinical interventions to preserve fertility and restore hormone levels in female patients with therapy-induced ovarian failure are insufficient, particularly for pediatric cancer patients. Laproscopic isolation of cortical ovarian tissue followed by cryopreservation with subsequent autotransplantation has temporarily restored fertility in at least 27 women who survived cancer, and aided in pubertal transition for one pediatric patient. However, reintroducing cancer cells through ovarian transplantation has been a major concern. Decellularization is a process of removing cellular material, while maintaining the organ skeleton of extracellular matrices (ECM). The ECM that remains could be stripped of cancer cells and reseeded with healthy ovarian cells. We tested whether a decellularized ovarian scaffold could be created, recellularized and transplanted to initiate puberty in mice. Bovine and human ovaries were decellularized, and the ovarian skeleton microstructures were characterized. Primary ovarian cells seeded onto decellularized scaffolds produced estradiol in vitro. Moreover, the recellularized grafts initiated puberty in mice that had been ovariectomized, providing data that could be used to drive future human transplants and have broader implications on the bioengineering of other organs with endocrine function.

Xenogeneic Decellularized Scaffold: A Novel Platform for Ovary Regeneration

“…[21][22][23][24] In 2015, the first D-ovary platform was successfully obtained and it partly restored endocrine functions in a mouse model. 15 However, some limitations existed in that method. First, the long SDS process has a strong damaging effect was demonstrated on the ultrastructure of the native tissue.…”

“…In 2015, decellularized ECM was successfully harvested from a bovine ovary for the first time. 15 The study provided the initial step of creating an artificial ovary and introduced a novel therapy for ovariectomized mice. However, longterm sodium dodecyl sulfate (SDS) treatment in the study has been reported to have a strong damaging effect on the ultrastructure of native tissue and be cytotoxic.…”

Comparison of Serum A Disintegrin and Metalloproteinase with Thrombospondin Motifs-19 Levels in Different Fertility Situations: Could It Be a Serum Marker of Ovarian Function and Oocyte Pool?

“…They stated that ECM enhances the growth and differentiation of the somatic cells of the follicle, also the meiotic competence of the oocyte, thus providing good quality eggs. Furthermore, it has been recently shown that ECM is a very important structure in maintaining follicle viability in terms of ovarian transplantation [20]. Decellularization made by leaving the ECM in place and followed by recellularization with primary ovarian cells was performed successfully in that experimental study.…”

Artificial Ovary

“…Laronda et al [46] constructed scaffolds from decellularized bovine and human ovarian tissue to graft primary murine ovarian cells. These recellularized matrices were able to initiate puberty in host ovariectomized mice.…”