Editors' ChoiceINFERTILITY

Tissue engineering the origins of life

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Science Translational Medicine  04 Mar 2015:
Vol. 7, Issue 277, pp. 277ec37
DOI: 10.1126/scitranslmed.aaa9496

Advances in drug discovery have dramatically improved the chances of survival for millions of children suffering from cancer. However, the benefits of these drugs are not without consequences. In addition to the harsh side effects incurred during treatment, toxic effects of drugs and radiation on female sex organs can lead to long-term problems with fertility, premature menopause, and impairment of the production of important hormones required for tissue maintenance. Currently, an experimental therapy involves removal of a patient’s ovarian tissue prior to chemotherapy and subsequent transplantation back into the same patient. Although this method has restored fertility in cancer survivors, the risk of reintroducing cancerous tissue is high.

To address these challenges, Laronda et al. developed a strategy to engineer an ovarian system that could restore systemic hormone regulation without the use of potentially cancerous tissue or cells. Indeed, the authors found evidence of cancerous cells in ovarian tissue obtained from leukemia patients, highlighting the need for an approach that avoids the patient’s own tissues. The team instead removed cells from human and bovine ovarian tissue while retaining the tissue extracellular matrix in a process known as decellularization. Ovarian cells from mice organized into ovarian tissue-like structures when seeded on the scaffolds, including follicle-like patterns and steroid blebs. When transplanted into prepubescent ovariectomized mice, the engineered tissues initiated puberty, as demonstrated by the presence of normal serum hormone levels as well as vaginal opening, a secondary sex characteristic. Amazingly, one engineered graft supported maturation of a follicle containing an oocyte.

This technology is still in its infancy, as its clinical translation would rely on induced pluripotent stem cells (iPSCs) to fully circumvent the introduction of potentially cancerous cells. Nonetheless, this study establishes proof-of-concept and adds to the growing body of evidence demonstrating the promise of tissue-engineered organs.

M. M. Laronda et al., Initiation of puberty in mice following decellularized ovary transplant. Biomaterials 50, 20–29 (2015). [Abstract]

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