Reconstruction of functional uterine tissues through recellularizing the decellularized rat uterine scaffolds by MSCs in vivo and in vitro

Abstract

Infertile people who suffered from loss of uterine structures and/or functions can be treated through gestational surrogacy or uterus transplantation, which remains challenging due to the ethical and social issues, the lack of donor organs as well as technical and safety risks. One promising solution is to regenerate and reconstruct a bioartificial uterus for transplantation through the engineering of uterine architecture and appropriate cellular constituents. Here, we developed a well-defined system to regenerate a functional rat uterine through recellularization of the decellularized uterine matrix (DUM) patches reseeded with human mesenchymal stem cells (hMSCs). Engraftment of the recellularized DUMs on the partially excised uteri yielded a functional rat uterus with a pregnancy rate and number of fetuses per uterine horn comparable to that of the control group with an intact uterus. Particularly, the recellularized DUMs enhanced the regeneration of traumatic uterine in vivo because of MSC regulation. The established system here will shed light on the treatment of uterine infertility with heterogeneous DUMs/cell resources through tissue engineering in the future.

Uterus bioengineering as a future alternative to uterus transplantation

“…The recellularized constructs were also able to restore fertility when the 10 mm × 5 mm rat uterus injury-and-repair model was used. Grafts were morphologically similar to native uterus tissue 90 days after transplantation, and interestingly, they found no signs of negative immunological response using GFP-labelled xenograft cells [37]. This study further supports the idea of using MSCs as an important immune modulator together with a biomaterial, and that this cell type might be used as a therapeutic mediator to stimulate endogenous repair mechanisms rather than trying to directly differentiate MSCs or other stem cells into mature uterus cells [38].…”

“…One recent publication used a grafting material based on SDS-based decellularized rat uterus tissue that were recellularized with GFP-labelled human MSCs [37]. Similar to the results presented in Hellström et al [34], few GFP-labelled cells survived more than seven days after engraftment.…”

Future Challenges and Opportunities of Extracellular Matrix Hydrogels in Female Reproductive Medicine

“…ECM products that are obtained from decellularization of female reproductive organs have salient roles in the field of reproductive medicine, with research focusing mainly on those that are derived from the uterus [ 51 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ], ovary [ 50 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ], cervix [ 93 ], vagina [ 94 , 95 ], and placenta [ 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. The variable methods that are used for decellularization are dependent on the tissue type and its characteristics.…”

“…Some groups employed reproductive ECM scaffolds as patches [ 67 , 68 , 77 , 79 ]. However, they offer the disadvantage of being applied invasively and they lack intense biochemical interaction with the transplantation site.…”

Human Endometrium‐Derived Adventitial Cell Spheroid‐Loaded Antimicrobial Microneedles for Uterine Regeneration

“…In previous studies, collagen scaffolds, decellularized uterine matrix, hydrogels, and synthetic polymer scaffolds have been applied to AS models, but mainly in an invasive manner, since the material itself does not have the ability to penetrate or adhere. [14][15][16][17][18] In this study, we established an adhesive antibacterial microneedle (MN) patch with a porous structure loaded with En-ADV spheroids (MN/En-ADV) to promote intrauterine regeneration in situ, as shown in Figure 1. The MN-based delivery system has been extensively investigated over the past four decades.…”