Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

Abstract BackgroundEndometrial injury contributes to impaired endometrial receptivity, and is well recognized as a critical factor in implantation failure. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSCs) mainly depend on their capacity to secrete paracrine factors and are mediated by MSC-derived exosomes (MSC-Exos). In this study, we aimed to explore the effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on injured endometrium in the mouse endometrial damage model and the potential mechanisms for these effects.MethodsAll female mice were randomly divided into control group, saline group, and exosome group. To observe the distribution of exosomes in vivo, DiR-labeled hUCMSC-Exos were injected into the tail vein of endometrium-injured mice. HE staining was used to detect changes in endometrial thickness and number of glands. TUNEL staining was used to detect cells apoptosis. The expression of Ki67 and CD31 was examined by immunohistochemistry. Then, western blotting was used to measure the expression of Bcl-2, Bax, Cleaved Caspase-3, PTEN, AKT and p-AKT. The expression of VEGF and IGF-1 was detected by RT-PCR.ResultshUCMSC-Exos was able to migrate to the damaged endometrium. After hUCMSC-Exos injection, the endometrial thickness and the number of glands were significantly increased (P< 0.05). Compared with the saline group, apoptosis was significantly reduced in the exosome group, and the expression of Ki67 and CD31 was significantly increased (P< 0.05). Besides, the expression of Bax, Cleaved Caspase-3 and PTEN was reduced as hUCMSC-Exos addition, and the Bcl-2 and p-Akt expression was increased. The expression of VEGF and IGF-1 was significantly upregulated in the exosome group compared to the saline group (P< 0.05).ConclusionshUCMSC-Exos ameliorated the damaged uterus, increased endometrial thickness, suppressed apoptosis and improved the cell proliferation in the mouse injured endometrium model. Furthermore, we discovered that hUCMSC-Exos could activate the PTEN/AKT signaling pathways and induce the overexpression of VEGF and IGF-1 in vivo.