Innovative Xenotransplantation of Reconstructed Human Artificial Ovary Using 3D-Printed Scaffolds and Umbilical Cord Mesenchymal Stem Cells Publisher



Ayoubipour M ; Eimani H ; Fathi R ; Shahverdi A ; Zarrabi M ; Kazemi Ashtiani M ; Tavana S ; Moosavi S A ; Tahaei L S ; Ghezelayagh Z ; Halvaei M ; Nouri M ; Golmohammadi Gerdkohi P ; Moini A
Source: International Journal of Fertility and Sterility Published:2026

Abstract

Background: The primary objective of this study was to develop an artificial ovary made of polylactic acid (PLA) material, which could potentially be used for fertility preservation. This scaffold was used to carry umbilical cord mesenchymal stem cells (UCMSCs) for xenotransplantation to study follicular growth, viability, and angiogenesis. Materials and Methods: The experimental study involved transplanting human ovarian cortical pieces into 3D-printed baskets, with or without human UCMSCs. Four groups were considered as control: vitrified-warmed ovarian tissue (OT), OT transplantation without 3D-printed baskets without UCMSCs, OT+D; OT transplantation with 3D-printed baskets and without UCMSCs, and OT+D+C; OT transplantation with 3D-printed baskets and UCMSCs. Eighteen rats were divided into three transplantation groups, with grafts implanted into their back muscles. After one week, comparisons were made between OT, OT+D, and OT+D+C with control groups. Histological evaluations and gene expression analyses, including CX37, CX43, KL, GDF9, and VEGF, were conducted to evaluate factors such as angiogenesis, cell proliferation, and follicle development. Results: The results revealed that OT+D had the highest follicular growth (99.3%) and transition rate (74.08%). OT+D+C indicated increased follicular survival, reduced mortality (P<0.0001), and a higher percentage of primordial follicles (59.1%) compared to OT and OT+D groups. UCMSCs’ paracrine secretions likely preserved the follicular reserve. Additionally, OT+D+C exhibited significantly increased blood vessel number and diameter (P<0.0001) compared to other groups. Conclusion: This study underscores the significance of utilizing a three-dimensional basket scaffold to enhance the development of ovarian follicles and facilitate angiogenesis. The integration of stem cells with the scaffold demon-strated a noteworthy synergistic effect, resulting in improved preservation and viability of the follicles and Reduced fibrosis. These findings illuminate the promising potential of scaffold-based strategies in advancing reproductive therapies and tissue engineering, thereby offering prospects for innovative treatments in the future. © 2026, Royan Institute (ACECR). All rights reserved.