Estrogen Secreted by Mesenchymal Stem Cells Necessarily Determines Their Feasibility of Therapeutical Application

Mesenchymal stem cells are therapeutically applicable and involved in the development of some types of diseases including estrogen (E2)-related ones. Little is known about E2 secretion by mesenchymal stem cells and its potential influence on their therapeutical applications. Our in vitro experiments showed that BMSCs cultured from C57BL/6J mice secreted E2 in a time-dependent manner. In vivo study identified a significantly increased E2 level in serum after a single administration of BMSCs, and a sustained elevation of E2 level upon a repetitive administration. Morris water maze test in the ovariectomised (OVX) mouse model revealed BMSCs transplantation ameliorated OVX-induced memory deficits by secreted E2. On the contrary, in endometriosis model, BMSCs transplantation aggravated endometriotic lesions because of E2 secretion. Mechanistically, the aromatase cytochrome P450 appeared to be critical for the biosynthesis and exerted effects of estrogen secretion by BMSCs. Our findings suggested that BMSCs transplantation is on the one hand an attractive option for the therapeutic treatment of diseases associated with E2 deficits in part through E2 secretion, on the other hand a detrimental factor for the E2-exasperated diseases largely via E2 production. It is important and necessary to monitor serum E2 level before and after the initiation of BMSCs therapy.