Improvement of Pregnancy Rate and Live Birth Rate in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived- Mesenchymal Stromal Cells: Phase I/II Clinical Trial

Zafardoust, Simin; Kazemnejad, Somaieh; Darzi, Maryam; Fathi-Kazerooni, Mina; Rastegari, Hilda; Mohammadzadeh, Afsaneh

doi:10.1007/s12015-020-09969-6

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…Secreted progesterone and estradiol increased in co-cultured murine preantral follicles and human MenSC implying a supportive role of MenSCs in follicle development, growth and maturation (Rajabi et al, 2018). In a recent clinical trial in 15 women, intraovarian injection of autologous MenSC in poor ovarian responders increased clinical pregnancy and live births (Zafardoust et al, 2020).…”

Section: Ovarian Function and Reservementioning

confidence: 95%

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Bozorgmehr

Gurung

Darzi

et al. 2020

Front. Cell Dev. Biol.

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Section: Ovarian Function and Reservementioning

confidence: 95%

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Bozorgmehr

Gurung

Darzi

et al. 2020

Front. Cell Dev. Biol.

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123

116

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“…MenSCs were manufactured as previously described [ 37 ]. MenSCs were culture-expanded from a previously established and characterized master cell bank (MCB) derived from the menstrual blood collected from at least 5 healthy women [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II

et al. 2022

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Background Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. Methods Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. Results All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). Conclusions For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. Trial registration: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287. IRCT, IRCT20180619040147N6. Registered 04/01/2021.

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“…DiI-labeled MenSCs were demonstrated to localize to granulosa cells of immature follicles [ 16 ]. Moreover, a recent clinical trial indicated that in poor ovarian responders, autologous MenSCs intraovarian injection could increase clinical pregnancy and live births rates [ 20 ]. Our previous study also indicated that MenSCs have reparative effects on cisplatin-induced premature ovarian failure mice.…”

Section: Introductionmentioning

confidence: 99%

FTO protects human granulosa cells from chemotherapy-induced cytotoxicity

Wang

et al. 2022

Reprod Biol Endocrinol

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Background Premature ovarian failure (POF) is a serious problem for young women who receive chemotherapy, and its pathophysiological basis is the dysfunction of granulosa cells. According to previous reports, menstrual-derived stem cells (MenSCs) can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Fat mass- and obesity-associated (FTO) was reported to be associated with oocyte development and maturation. FTO was decreased in POF and may be a biomarker for the occurrence of POF. Knockdown of FTO in granulosa cells promoted cell apoptosis and inhibited proliferation. But the relationship between FTO and ovarian repair was still unclear. This study was aimed at investigating the FTO expression level and the role of FTO in the MenSCs recovering the function of injured granulosa cells. Method First, cisplatin was used to establish a granulosa cell injury model. Then, the MenSCs and injured granulosa cell coculture model and POF mouse model were established in this study to explore the role of FTO. Furthermore, gain- and loss-of-function studies, small interfering RNA transfection, and meclofenamic acid (MA), a highly selective inhibitor of FTO, studies were also conducted to clarify the regulatory mechanism of FTO in granulosa cells. Results MenSCs coculture could improve the function of injured granulosa cells by increasing the expression of FTO. MenSCs transplantation restored the expression of FTO in the ovaries of POF mice. Overexpression of FTO restored the injured cell proliferation and decreased apoptosis by regulating the expression of BNIP3. Down-regulation of FTO got the opposite results. Conclusions In the treatment of MenSCs, FTO has a protective effect, which could improve the viability of granulosa cells after cisplatin treatment by decreasing the expression of BNIP3. Meanwhile, FTO may provide new insight into therapeutic targets for the chemotherapy-induced POF.

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Improvement of Pregnancy Rate and Live Birth Rate in Poor Ovarian Responders by Intraovarian Administration of Autologous Menstrual Blood Derived- Mesenchymal Stromal Cells: Phase I/II Clinical Trial

Cited by 24 publications

References 34 publications

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II

FTO protects human granulosa cells from chemotherapy-induced cytotoxicity

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