Abstract
Human placental mesenchymal stem cells (hPMSCs) have the ability to release cytokines and to differentiate into the three germ layers. To date, the relevance of hPMSCs for the treatment of premature ovarian insufficiency (POI) disease through the regulation of oxidative stress is still unclear. Therefore, to evaluate the therapeutic efficiency and investigate the mechanism of hPMSCs, we generated a mouse model of POI and collected human ovarian granule cells (hGCs) from patients with POI. hPMSCs displayed therapeutic effects on POI ovarian function, including recovered follicular numbers and increased expression of oocyte markers. Furthermore, secretion of the cytokine EGF (epidermal growth factor) was higher from hPMSCs than it was from other cells. FACS and Western blot analyses showed that EGF elevated the proliferation and reduced the apoptosis in hGCs. hPMSCs and EGF inhibited oxidative stress levels. Protein assays demonstrated that EGF suppressed oxidative stress by dose-dependently upregulating the expression of the NRF2/HO-1 pathway, and it inhibited the apoptosis by regulating the PTEN/PI3K/AKT pathway. These findings provide an experimental foundation for hPMSCs in improving ovarian function through the secretion of EGF. The mechanism of action of EGF is related to protection from oxidative stress by activation of the NRF2/HO-1.
Highlights
Current epidemiological data show that the ovary plays a vital role in regulating metabolic and physiological functions in women [1]
Our results indicated high expression of cell surface markers CD29, CD73 and CD90 and minimal expression of CD105 and CD34 in Human placental mesenchymal stem cells (hPMSCs) (Supplementary Figure 1A). hPMSCs with the capacity to differentiate into adipocytes, chondroblasts and osteoblasts have been demonstrated to be multipotent mesenchymal stem cells (Supplementary Figure 1B)
Ovarian tissues were hematoxylin and eosin (HE) stained, and the results revealed that the follicle number was significantly restored by treatment with hPMSCs and hPMSCs-Conditioned medium (CM) at the fourth week (Figure 1A–1D)
Summary
Current epidemiological data show that the ovary plays a vital role in regulating metabolic and physiological functions in women [1]. DNA damage can accumulate over time, but in resting cells, such as human granule cells (hGCs) or primordial follicles, there is the inability to eliminate faulty cells during replication, which results in premature ovarian failure [3]. MSCs can alleviate tissue damage by stimulating the recruitment and proliferation of endogenous stem cells, inhibiting fibrotic remodeling and apoptosis, promoting antiapoptotic activity, and reducing the immune response [7]. The characteristics of poor immunogenicity and stable proliferation make hPMSCs a new source of stem cells that are suitable for cell therapy. Their non injurious property holds substantial prospects self-repair of cells and regeneration. EGF family members promote growth and differentiation of recruited primordial follicles in late folliculogenesis [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
