Initiation of puberty in mice following decellularized ovary transplant.
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 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.
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Monica M
MM
Laronda
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
Adam E
AE
Jakus
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Kelly A
KA
Whelan
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Surgery, Jesse Brown VA Medical Center, Chicago, IL, USA; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Jason A
JA
Wertheim
Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA; Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Ramille N
RN
Shah
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: tkw@northwestern.edu.
Teresa K
TK
Woodruff
D000293:Adolescent; D000328:Adult; D000818:Animals; D001706:Biopsy; D002417:Cattle; D045744:Cell Line, Tumor; D002648:Child; D004958:Estradiol / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation* / Q000648:ultrastructure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D012741:Sexual Maturation / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism
C472575:SALL4 protein, human; D014157:Transcription Factors; D004958:Estradiol
Bioactivity; Decellularization; ECM (extracellular matrix); Endocrine function; SEM (scanning electron microscopy); Xenotransplantation