Human Mesenchymal Stem Cell Therapy and Other Novel Treatment Approaches for Premature Ovarian Insufficiency

Ulin, Mara; Çetin, Esra; Hobeika, Elie; Chugh, Rishi Man; Park, Hang-Soo; Esfandyari, Sahar; Al-Hendy, Ayman

doi:10.1007/s43032-021-00528-z

Cited by 20 publications

(16 citation statements)

References 65 publications

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“…But long-term HRT also has certain risks, such as the occurrence of endometrial cancer and breast cancer [1]. Mesenchymal stem cell transplantation is considered to be a very promising treatment strategy for reversing the negative effects of POI [3] . One of the key events that contribute to ovarian aging includes follicular atresia as it is associated with the pyroptosis and necrosis of granulosa cells and thecal cells in aging ovaries.…”

Section: Discussionmentioning

confidence: 99%

“…Hormone replacement therapy, as a rst-line clinical treatment, can reduce the symptoms caused by estrogen de ciency, but there is still no method for restoring follicular development in failed ovaries [2] . In recent years, many studies have suggested that transplantation of stem cells may be able to restore ovarian function [3] . When mesenchymal stem cells (MSCs) were used to treat POI, there was a decrease in apoptosis of ovarian granulosa cells (GCs), recovery of ovarian function, and increased levels of sex hormones [4][5][6][7] ; however, the underlying mechanism remained elusive.…”

Section: Introductionmentioning

confidence: 99%

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Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Xing

et al. 2022

Preprint

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Background Premature ovarian insufficiency (POI) is a common clinical problem but there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. Methods Female Sprague–Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. Results VCD significantly damaged the rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs could remarkably suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1β and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors. Conclusions Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Xing

et al. 2022

Preprint

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“…The mechanism underlying the developmental progression of human primordial follicles is unclear. However, the initial recruitment has been linked to protein kinase B (Akt) and mammalian target of rapamycin (mTOR) signaling pathways [ 6 , 22 ].…”

Section: Premature Ovarian Insufficiency (Poi)mentioning

confidence: 99%

Therapeutic Effect of Melatonin in Premature Ovarian Insufficiency: Hippo Pathway Is Involved

Sun

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. Premature ovarian insufficiency (POI) is a female reproductive disorder of unknown etiology with no definite pathogenesis. Melatonin (MT) is an endogenous hormone synthesized mainly by pineal cells and has strong endogenous effects in regulating ovarian function. To systematically explore the pharmacological mechanism of MT on POI therapy, a literature review approach was conducted at the signaling pathways level. Methods. Relevant literatures were searched and downloaded from databases, including PubMed and China National Knowledge Infrastructure, using the keywords “premature ovarian insufficiency,” “Hippo signaling pathways,” and “melatonin.” The search criteria were from 2010 to 2022. Text mining was also performed. Results. MT is involved in the regulation of Hippo signaling pathway in a variety of modes and has been correlated with ovarian function. Conclusions. The purpose of this review is to summarize the research progress of Hippo signaling pathways and significance of MT in POI, the potential crosstalk between MT and Hippo signaling pathways, and the prospective therapy.

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“…For example, Yan et al transplanted MSCs to 61 patients with POF and found that the number of follicles in each developmental stage, including antral follicles, dominant follicles and mature follicles, increased significantly ( Yan et al, 2020 ). Other researchers have found that autologous MSC transplantation can trigger menstruation to resume, relieve menopausal symptoms, improve ovarian function and help patients become pregnant ( Bukovsky and Caudle, 2012 ; Igboeli et al, 2020 ; Mashayekhi et al, 2021 ; Ulin et al, 2021 ). Ling et al treated POF mice with MSCs and found that MSC transplantation could significantly restore their hormone secretion ability, improve follicular growth and GC survival, and recover the ovarian function that was destroyed by chemotherapy used to create the POF mice ( Ling et al, 2019 ).…”

Section: Mscs and Fertility Protectionmentioning

confidence: 99%

Research Progress on the Treatment of Premature Ovarian Failure Using Mesenchymal Stem Cells: A Literature Review

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Premature ovarian failure (POF) has become one of the main causes of infertility in women of childbearing age and the incidence of POF is increasing year by year, seriously affecting the physical and mental health of patients and increasing the economic burden on families and society as a whole. The etiology and pathogenesis of POF are complex and not very clear at present. Currently, hormone replacement therapy is mainly used to improve the symptoms of low estrogen, but cannot fundamentally solve the fertility problem. In recent years, stem cell (SC) transplantation has become one of the research hotspots in the treatment of POF. The results from animal experiments bring hope for the recovery of ovarian function and fertility in patients with POF. In this article, we searched the published literature between 2000 and 2020 from the PubMed database (https://pubmed.ncbi.nlm.nih.gov), and summarized the preclinical research data and possible therapeutic mechanism of mesenchymal stem cells (MSCs) in the treatment of POF. Our aim is to provide useful information for understanding POF and reference for follow-up research and treatment of POF.

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Human Mesenchymal Stem Cell Therapy and Other Novel Treatment Approaches for Premature Ovarian Insufficiency

Cited by 20 publications

References 65 publications

Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Placental mesenchymal stem cells improve ovarian function in a rat model of premature ovarian insufficiency by inhibiting NLRP3 inflammasome activity

Therapeutic Effect of Melatonin in Premature Ovarian Insufficiency: Hippo Pathway Is Involved

Research Progress on the Treatment of Premature Ovarian Failure Using Mesenchymal Stem Cells: A Literature Review

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