As a refractory fibrosis disease, intrauterine adhesions (IUAs) is defined as fibrosis of the physiological endometrium. Although hysteroscopic adhesiolysis is widely recommended as an effective treatment, prognosis and recurrence remain poor in severe cases. Recently, stem cell therapy has been promoted as a promising treatment for IUAs. The ability of human amniotic epithelial cells (hAECs), emerging as a new candidate for stem cell therapy, to treat IUAs has not been demonstrated. To study the potential effects of hAECs on IUAs, we created an IUA rat model using mechanical injury and injected cultured primary hAECs into the rats' uteri. Next, we observed the morphological structure of endometrial thickness and glands using hematoxylin and eosin staining, and we detected extracellular-matrix collagen deposition using Masson staining. In addition, we performed immunohistochemical staining and reverse-transcription polymerase chain reaction (RT-PCR) to investigate potential fibrosis molecules and angiogenesis factors 7 d after hAECs transplantation. Finally, we detected estrogen receptor (ER) and growth factors via RT-PCR to verify the molecular mechanism underlying cell therapy. In the IUA rat models, endometrial thickness and endometrial glands proliferated and collagen deposition decreased significantly after hAEC transplantation. We found that during the recovery of injured endometrium, the crucial fibrosis marker transforming growth factor-β (TGF-β) was regulated and angiogenesis occurred in the endometrial tissue with the up-regulation of vascular endothelial growth factor. Furthermore, hAECs were shown to promote ER expression in the endometrium and regulate the inflammatory reaction in the uterine microenvironment. In conclusion, these results demonstrated that hAEC transplantation could inhibit the progression of fibrosis and promote proliferation and angiogenesis in IUA rat models. The current study suggests hAECs as a novel stem cell candidate in the treatment of severe IUA.
Keywords: angiogenesis; cell therapy; human amniotic epithelial stem cells; intrauterine adhesions; transforming growth factor-β.