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. Laparoscopic 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 invitro. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 20-29 |
| Number of pages | 10 |
| Journal | Biomaterials |
| Volume | 50 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
Funding
This work is supported by the Watkins Chair of Obstetrics and Gynecology (TKW), the UH3TR001207 ( NCATS , NICHD , NIEHS , OWHR , NIH Common Fund ) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development U54HD076188 grant. The Oncofertility Consortium ® is funded by the National Institutes of Health through the NIH Roadmap for Medical Research , Grant UL1DE19587 and PL1CA133835 . JAW acknowledges support from K08DK101757. This work made use of the EPIC facility (NUANCE Center – Northwestern University), which has received support from the MRSEC program ( NSF DMR-0520513 ) at the Materials Research Center, The Nanoscale Science and Engineering Center ( EEC-0118025|003 ), both programs of the National Science Foundation; the state of Illinois; and Northwestern University. This work was supported by the Northwestern University Mouse Histology and Phenotyping Laboratory and a Cancer Center Support Grant ( NCI CA060553 ). The authors thank Alan Conley for the generous use of the Cyp17α antibody and the late Dr. Wylie Vale and Dr. Joan Vaughan, Salk Institute for the use of anti-inhibin A. We also thank Megan Romero and Keisha Barreto from the Ovarian Histology Core at Northwestern University for their technical expertise.
Keywords
- Bioactivity
- Decellularization
- ECM (extracellular matrix)
- Endocrine function
- SEM (scanning electron microscopy)
- Xenotransplantation
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Ceramics and Composites
- Biomaterials
- Mechanics of Materials
