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Estrogen Secreted by Mesenchymal Stem Cells Necessarily Determines Their Feasibility of Therapeutical Application
Jiansha Li1,2, Xiaochun Peng1, Xianqin Zeng1
1Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine.
Abstract:
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.
Insights
Mesenchymal stem cells secrete estrogen (E2), which can improve memory deficits in ovariectomized mice but worsen endometriosis. Aromatase is key to this E2 production, necessitating E2 monitoring during stem cell therapy.
Area of Science:
- Stem Cell Biology
- Endocrinology
- Reproductive Medicine
Background:
- Mesenchymal stem cells (MSCs) have therapeutic potential but their role in estrogen (E2)-related diseases is unclear.
- Estrogen secretion by MSCs and its impact on therapeutic applications require further investigation.
Purpose of the Study:
- To investigate estrogen secretion by bone marrow-derived MSCs (BMSCs) and its dual role in disease models.
- To elucidate the mechanism of E2 production by BMSCs and its therapeutic implications.
Main Methods:
- In vitro culture of mouse BMSCs to assess time-dependent E2 secretion.
- In vivo studies in ovariectomized (OVX) and endometriosis mouse models.
- Morris water maze test for cognitive function assessment.
- Measurement of serum E2 levels and analysis of aromatase cytochrome P450 involvement.
Main Results:
- BMSCs secreted E2 in vitro in a time-dependent manner.
- BMSC administration increased serum E2 levels in vivo, sustained with repetitive dosing.
- BMSC transplantation ameliorated OVX-induced memory deficits, mediated by secreted E2.
- BMSC transplantation aggravated endometriosis lesions due to E2 secretion.
- Aromatase cytochrome P450 was identified as critical for E2 biosynthesis and secretion by BMSCs.
Conclusions:
- BMSC transplantation offers therapeutic benefits for E2-deficient conditions via E2 secretion.
- BMSC transplantation can be detrimental in E2-exacerbated diseases due to E2 production.
- Monitoring serum E2 levels before and after BMSC therapy is crucial.
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