Transplantation of Human Adipose Stem Cells Using Acellular Human Amniotic Membrane Improves Angiogenesis in Injured Endometrial Tissue in a Rat Intrauterine Adhesion Model

Endometrial injury resulting in intrauterine adhesion is associated with extensive damage to the regenerative basal layer of the endometrium and represents a major therapeutic challenge. Human adipose stem cells (hASCs) hold promise for future clinical use in the individualized therapy of injured endometrial tissue. Here, we observed that the use of the acellular human amniotic membrane (AHAM) significantly increased the expression of angiogenic factors, including angiogenin (ANG) and vascular endothelial growth factor (VEGF), in hASCs in vitro. The three-dimensional engineered hASC-AHAM grafts significantly increased the endometrial receptivity, as increased endometrial thickness, greater numbers of endometrial glands, and higher protein levels of leukemia inhibitory factor were observed in injured endometrial tissue that was treated with these grafts compared to those detected in injured endometrial tissue that was treated with AHAM alone. In addition, the hASC-AHAM grafts significantly increased the vascular density in the injured endometrial tissue in rats, when transplanted into an injured uterine cavity. Using the EGFP+-hASC-AHAM grafts for transplantation, we confirmed that the hASCs maintained higher protein levels of ANG and VEGF in the injured uterine cavity in vivo. The results of this study suggest that the ability of the engineered hASC-AHAM grafts to repair injured endometrial tissue may be associated with their ability to promote angiogenesis through the upregulated expression of angiogenic factors in hASCs. These findings may support individualized stem cell–based therapy for endometrial disease using bioartificial grafts.