Human Endometriosis Scaffold Can Enhance Cell Seeding and Engraftment; an In Vitro and In Vivo Study

The extracellular matrix (ECM) critically influences cell behavior, yet its properties in human endometrial lesions (HEL) and human uterine fibromas (HUF) are not well characterized. This study aimed to characterize their ECM and evaluate its impact on cell engraftment and proliferation while optimizing a decellularization protocol. HEL and HUF tissues, collected during laparoscopic surgeries, were decellularized using a novel protocol. Complete cell removal and preserved ECM microstructure were confirmed by histology, DAPI, Masson's trichrome staining and scanning electron microscopy. The decellularized scaffolds were used as a platform for three-dimensional culture of human endometrial-derived mesenchymal stem cells (hEMSCs), with HUF serving as a fibrotic control originated from the same organ system. The biological impact of the ECM was assessed via immunohistochemistry for engraftment marker matrix metalloproteinase-9 and proliferation marker antigen Kiel-67. The in vivo recellularization potential of HEL scaffolds was further evaluated in a rat model, with HEL scaffold group at two timepoints (n = 6/group) and a sham control (n = 3). Results confirmed complete decellularization with maintained ECM integrity in both HEL and HUF. In vitro evaluation indicated that hEMSCs seeded more efficiently onto HEL scaffolds (51.16 ± 28.84) compared to HUF scaffolds (6.16 ± 7.29) (p = 0.012). The in vivo peritoneal implanted HEL scaffolds demonstrated significant time-dependent host cell recruitment and remodeling compared to the sham control. In conclusion, the decellularized HEL scaffold provides a superior ECM platform for cell seeding and engraftment compared to HUF, making it a promising platform for modeling endometriosis in both in vitro and in vivo settings.