Progress in Preclinical Research on Uterus Bioengineering That Utilizes Scaffolds Derived from Decellularized Uterine Tissue

Abstract

During the last decade, uterus transplantation has evolved as the first treatment for absolute uterine factor infertility, caused by absence of a functional uterus. Current challenges in the area of uterus transplantation are organ shortage and side effects of immunosuppression. These hurdles may be solved with novel tissue engineering technologies to produce a uterus from stem cells. For example, the development of patient-specific grafts using a biomaterial together with the patient’s own cells might be utilized for a partial uterus repair therapy or a whole bioengineered uterus might be developed to replace an allogeneic graft in a uterus transplantation setting. During recent years, uterus bioengineering strategies with scaffolds based on decellularized tissue have been particularly assessed. Decellularization protocols were established for both small and large animal models, including the human uterus. Promising in vivo results using such scaffolds to repair a partially injured uterus showed restoration of fertility in rodent models. Scaffold generation protocols and recellularization methodologies including various cell sources are currently being optimized and translated to more clinically relevant injury models in large animals. This review provides a summary of the progress made to date, based on use of decellularized uterine tissue for uterus repair.

Transplantation of a bioengineered tissue patch promotes uterine repair in the sheep

“…In this study, we extended the translational relevance of previous uterus bioengineering research that, to date, only used small animal models for in vivo proof-of-concept studies. 8,31 Herein, the methodology was applied to the sheep model with a uterine size similar to the human. Our primary objective was to evaluate the feasibility of a bioengineered uterus patch for a tissue replacement therapy in a large animal model, a strategy that may ultimately result in a new fertility restauration treatment for women with acquired uterine defects.…”

“…6 Bioengineered reproductive tissues may be derived from extracellular matrix (ECM) scaffolds obtained from respective decellularized tissue. 7,8 Pioneering uterus bioengineering work in a rat model indicated how such scaffolds entail a therapeutic alternative to regenerate damaged uterine tissue in a situation of significant defects following multiple cesarean sections or extensive myomectomy that causes infertility. [9][10][11] Extracellular matrix-derived scaffolds provide bioactive cues, structural support, and a low immuno-genicity, making them suitable for transplantation.…”