Initiation of puberty in mice following decellularized ovary transplant

被引:154
作者
Laronda, Monica M. [1 ]
Jakus, Adam E. [2 ,3 ]
Whelan, Kelly A. [1 ]
Wertheim, Jason A. [2 ,4 ,5 ,6 ,7 ,8 ]
Shah, Ramille N. [2 ,3 ,4 ,5 ]
Woodruff, Teresa K. [1 ]
机构
[1] Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Div Reprod Biol, Chicago, IL 60611 USA
[2] Northwestern Univ, Simpson Querrey Inst BioNanotechnol, Chicago, IL 60611 USA
[3] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA
[4] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA
[5] Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA
[6] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA
[7] Northwestern Univ, Chem Life Proc Inst, Evanston, IL USA
[8] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Bioactivity; Decellularization; Endocrine function; ECM (extracellular matrix); SEM (scanning electron microscopy); Xenotransplantation; EMBRYONIC STEM-CELLS; FEMALE SURVIVORS; TISSUE; FERTILITY; THERAPY; CANCER; DIFFERENTIATION; INFERTILITY; ESTROGEN; CHEMOTHERAPY;
D O I
10.1016/j.biomaterials.2015.01.051
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:20 / 29
页数:10
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