Adipose-Derived Mesenchymal Stem Cell Transplantation in Chemotherapy-Induced Premature Ovarian Insufficiency: the Role of Connexin and Pannexin

Halicioğlu, Büşra Şen; Saadat, Khandakar A.S.M.; Tuğlu, Mehmet İbrahim

doi:10.1007/s43032-021-00718-9

Cited by 14 publications

(7 citation statements)

References 58 publications

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“…Human mesenchymal stem cell therapy is a novel strategy for retain ovarian function and treat female infertility [ 17 ]. Available hMSCs include human bone marrow-derived mesenchymal stem cells, human adipose tissue-derived stem cells, and human amniotic membrane mesenchymal stem cells [ 18 , 19 ]. However, problems such as embolism, immunogenicity, malignant transformation, poor cell engraftment and post-transplantation survival limit the application of stem cell therapy [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Zhou,

Huang,

Zeng

et al. 2024

J Ovarian Res

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Background Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. Methods hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. Results hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. Conclusion hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.

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Section: Discussionmentioning

confidence: 99%

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Zhou,

Huang,

Zeng

et al. 2024

J Ovarian Res

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“…ADMSCs can increase levels of transforming growth factor-beta1 and interleukin-10 in serum, resulting in expansion of the regulatory T cell population, thereby regulating immune functions and restoring ovarian function in POF[ 22 ]. Furthermore, ADMSC transplantation exerts an anti-apoptotic effect by modulating connexin 43 and pannexin 1 during the treatment of POI[ 23 ]. Co-culturing the extracellular vesicles of ADMSCs with GCs from women with POI has been found to promote cell proliferation, downregulate suppressor of mothers against decapentaplegic family protein expression, and inhibit the expression of genes associated with GC apoptosis[ 24 ].…”

Section: Adipose-derived Mscsmentioning

confidence: 99%

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics

Hu,

Xin,

Zhu

et al. 2024

World J Stem Cells

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The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

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“…In the scenario of animal reproduction, a study conducted in rats demonstrated that the application of MSCs was able to increase the expression of genes related to vascular endothelium growth in ovarian tissue, besides indicating a high concentration of MSCs in the theca and primordial follicle regions (Vural et al, 2019). Another treatment performed with MSCs was able to increase the concentrations of estrogen (E2) and anti-Müllerian hormone (AMH) in rats affected by ovarian insufficiency (Feng et al, 2020;Sen Halicioglu et al, 2022), demonstrating both the hormonal and tissue applicability that cellular treatment can have in animal reproduction.…”

Section: /14mentioning

confidence: 99%

Mesenchymal stem cells in animal reproduction: sources, uses and scenario

Oliveira,

Braga,

Miranda

et al. 2024

Braz. J. Vet. Med.

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Studies regarding mesenchymal stem cells turned up in the 1960's and this cell type created a great number of questions about its functions and applicability in science and medicine. When used with therapeutic intent, these cells present an inclination to migrate to sites of injury, inflammation or disease, where they secrete bioactive factors that stimulates the synthesis of new tissue. In this context, studies using rodents reported that MSCs promoted positive effects in the ovarian function in mice with premature aging of follicular reserve. In female bovines, experimental stem cell-based therapies have been used to either generate new oocytes with in vitro quality or stimulate such action in vivo. It is also reported, that the intraovarian application of mesenchymal stem cells generates a greater production of embryos in vitro and the production of early and expanded blastocysts. Additionally, analysis of ovarian tissue in animal subjected to treatment showed an increase in the number of developing follicles. Nevertheless, the treatments involving stem cells with different modes of application, different sources and different species were able to act on the hormonal, tissue, cellular and metabolic levels, generating positive results in the recovery and improvement of ovarian functions.

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Adipose-Derived Mesenchymal Stem Cell Transplantation in Chemotherapy-Induced Premature Ovarian Insufficiency: the Role of Connexin and Pannexin

Cited by 14 publications

References 58 publications

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics

Mesenchymal stem cells in animal reproduction: sources, uses and scenario

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