Partial regeneration and reconstruction of the rat uterus through recellularization of a decellularized uterine matrix.

Abstract

Despite dramatic progress in infertility treatments and assisted reproduction, no effective therapies exist for complete loss of uterine structure and/or function. For such patients, genetic motherhood is possible only through gestational surrogacy or uterine transplantation. However, many ethical, social, technical and safety challenges accompany such approaches. A theoretical alternative is to generate a bioartificial uterus, which requires engineering of uterine architecture and appropriate cellular constituents. Here, rat uteri decellularization by aortic perfusion with detergents produced an underlying extracellular matrix together with an acellular, perfusable vascular architecture. Uterine-like tissues were then regenerated and maintained in vitro for up to 10 d through decellularized uterine matrix (DUM) reseeding with adult and neonatal rat uterine cells and rat mesenchymal stem cells followed by aortic perfusion in a bioreactor. Furthermore, DUM placement onto a partially excised uterus yielded recellularization and regeneration of uterine tissues and achievement of pregnancy nearly comparable to the intact uterus. These results suggest that DUM could be used for uterine regeneration, and provides insights into treatments for uterine factor infertility.