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PLoS One. 2014 Jul 24;9(7):e103201. doi: 10.1371/journal.pone.0103201. eCollection 2014.

Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models.

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Department of Mechanical Engineering, School of Engineering, The University of Tokyo, Tokyo, Japan.
Department of Obstetrics and Gynecology, School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Department of Material-based Medical Engineering, Division of Biofunctional Restoration, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Mechanical Engineering, School of Engineering, The University of Tokyo, Tokyo, Japan; Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.


Infertility caused by ovarian or tubal problems can be treated using In Vitro Fertilization and Embryo Transfer (IVF-ET); however, this is not possible for women with uterine loss and malformations that require uterine reconstruction for the treatment of their infertility. In this study, we are the first to report the usefulness of decellularized matrices as a scaffold for uterine reconstruction. Uterine tissues were extracted from Sprague Dawley (SD) rats and decellularized using either sodium dodecyl sulfate (SDS) or high hydrostatic pressure (HHP) at optimized conditions. Histological staining and quantitative analysis showed that both SDS and HHP methods effectively removed cells from the tissues with, specifically, a significant reduction of DNA contents for HHP constructs. HHP constructs highly retained the collagen content, the main component of extracellular matrices in uterine tissue, compared to SDS constructs and had similar content levels of collagen to the native tissue. The mechanical strength of the HHP constructs was similar to that of the native tissue, while that of the SDS constructs was significantly elevated. Transmission electron microscopy (TEM) revealed no apparent denaturation of collagen fibers in the HHP constructs compared to the SDS constructs. Transplantation of the decellularized tissues into rat uteri revealed the successful regeneration of the uterine tissues with a 3-layer structure 30 days after the transplantation. Moreover, a lot of epithelial gland tissue and Ki67 positive cells were detected. Immunohistochemical analyses showed that the regenerated tissues have a normal response to ovarian hormone for pregnancy. The subsequent pregnancy test after 30 days transplantation revealed successful pregnancy for both the SDS and HHP groups. These findings indicate that the decellularized matrix from the uterine tissue can be a potential scaffold for uterine regeneration.

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