Uterine Tissue Engineering and the Future of Uterus Transplantation

Abstract

The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

“…Today, uterus transplantation is an available therapy for absolute uterine factor infertility . However, immunological rejection and critical shortage of donor organs restrict its popularization . At present, we use intrauterine device with high doses of estrogen to prevent intrauterine adhesion (IUA) and promote endometrium regeneration after surgical synechiotomy in clinic .…”

“…Self‐refreshable BMSCs with multidifferential potential are readily available and could be autotransplanted without immunologic rejection, showing advantages in the repair and restoration of tissues and organs . Cell therapies for treating AS mainly focused on biological collagen with cells to replenish the cellular compartments . Transplantation of collagen/BMSCs promotes the proliferation of endometrial and muscular cells, and recovers the capacity of endometrium to support the location and maturation of the embryos .…”

Organs-On-Chip Models of the Female Reproductive System

“…In this sense, in our opinion, techniques and methods from the field of regenerative medicine and tissue engineering could improve the performance and the functions of the reproductive OoC platforms discussed above. Materials and designs are used in reconstructive surgery [39], organ transplantation [40], study of endometrial physiology and differentiation [37,41] and development of 3D models of the reproductive organs for in vitro studies [41,42].…”

Uterus transplantation: Toward clinical application in Japan

“…In addition, the ELSI for progressive medical performance will change over time. Furthermore, uterine tissue engineering has been tried in rat models . If the artificial uterus or placenta is able to regenerate, UTx might become unnecessary for the treatment of UFI.…”