Abstract
The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.
Highlights
The endometrium is a highly regenerative tissue, which undergoes monthly growth, differentiation, and shedding during a woman’s reproductive years
HUCMSC-Exos were prepared for the following experiments: Exosomes were characterized by negative-staining electron microscopy and western blotting according to their size and surface marker expression
A negative correlation between PTEN and p-AKT expression was observed. These results demonstrated that hUCMSC-Exos could induce the overexpression of p-AKT and activate the PTEN/AKT signaling pathway which could regulate cell growth, migration, and angiogenesis, and this effect was partly weakened by the PTEN/AKT pathway inhibitor
Summary
The endometrium is a highly regenerative tissue, which undergoes monthly growth, differentiation, and shedding during a woman’s reproductive years. Human endometrial stromal cells play an essential role in maintaining endometrial homeostasis [1]. Studies supported that hEndoSCs were responsible for endometrial decidualization, vascular reconstruction, immune cell recruitment, and plentiful molecule production, which play a critical role in repairing endometrial injury [2]. Endometrial injury activates apoptotic signaling pathways, inhibits endometrial angiogenesis, and hinders endometrial regeneration. Mesenchymal stem cells (MSCs) have self-renewal and multipotential differentiation properties and are widely applied into the stem cell therapy [4]. MSCs derived from umbilical cord, one of the abundant sources of MSCs, provide a safe and low immunogenic alternative source of tissue regenerating after endometrial injury [5, 6].
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