Abstract
BackgroundYoung female patients who receive chemotherapy frequently face premature ovarian failure (POF). The therapeutic potential of stem cells in these patients has been explored in stem cells derived from different sources. However, many of these types of stem cells are either difficult to obtain or obtaining them involves invasive procedures. Here, we show that menstrual-derived stem cells (MenSCs) are easy to access and exhibit mesenchymal stem cell-like properties. MenSCs are therefore a novel source of stem cells that can be used for tissue repair. The aim of this study was to explore the reparative capacity and the mechanism underlying the activities of MenSCs.MethodsPOF mouse models were established by 7 consecutive days of intraperitoneal injection of cisplatin, and then MenSCs or MenSC-derived conditioned media (CM) were infused via the tail vein. The ovaries were excised after either 7 or 21 days of treatment and the follicles were counted and categorized. Apoptosis of granulosa cells was observed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling staining. Ovarian function was evaluated by monitoring serum sex hormone levels. Furthermore, MenSC tracking, Q-PCR, and small interfering RNA transfection were used to reveal the inner mechanism of repair.ResultsMenSC transplantation could improve the ovarian microenvironment by reducing apoptosis in granulosa cells and the fibrosis of ovarian interstitium, which contributes to increase the follicular numbers and return sex hormone levels to normal values. Meanwhile, the transplanted MenSCs directively migrate to ovarian interstitium to play a role in repair rather than differentiate to oocytes directly. Additionally, MenSCs and CM derived from these cells exerted protective effects on damaged ovaries partially by secreting FGF2.ConclusionMenSCs repair ovarian injury, improve ovarian function, and stimulate regeneration, suggesting that transplantation of MenSCs may provide an effective and novel method for treating POF.
Highlights
Young female patients who receive chemotherapy frequently face premature ovarian failure (POF)
The side effects caused by chemotherapy include damage to the ovaries in female patients, and this effect cannot be ignored because it frequently leads to premature ovarian failure/insufficiency (POF/POI) or menopause as a direct result of its toxic
transferase mediated dUTP nick end labelling (TUNEL)-positive GCs were clearly observed in the POF group, and the results suggested that apoptosis was largely restricted to the GC layer of follicles, in close proximity to the oocytes
Summary
Young female patients who receive chemotherapy frequently face premature ovarian failure (POF). The therapeutic potential of stem cells in these patients has been explored in stem cells derived from different sources Many of these types of stem cells are either difficult to obtain or obtaining them involves invasive procedures. Interest has rapidly grown in studies exploring the therapeutic potential of stem cells because of their potential to differentiate into various specialized cell types This characteristic has been observed in stem cells derived from a number of different sources, including bone marrow [6,7,8], amniotic fluid [9], and adipose tissue [10, 11], and all of these cell types have been shown to have therapeutic effects on long-term infertility and ovarian damage. Many of the suitable cell types currently identified for human use are either difficult to obtain or obtaining them involves invasive procedures
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