Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN

Yang, Meiling; Lin, Li; Sha, Chunli; Li, Taoqiong; Zhao, Dan; Wei, Hong; Chen, Qi; Liu, Yueqin; Chen, Xiaofang; Xu, Wenlin; Li, Yuefeng; Zhu, Xiaolan

doi:10.1038/s41374-019-0321-y

Cited by 153 publications

(117 citation statements)

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“…Despite having the ability to differentiate into many other cell types under targeted lineage-specific culture conditions, stem cells have shown promising results in curing diseases by their direct insertion into disease models. A number of neonatal and adult sources including bone marrow [43,47,48,55,108,109], endometrial [110], amnion [53,111], amniotic fluid [4], amniotic epithelium [44], menstrual blood [9,51], umbilical cord [56,112], umbilical cord blood [54], umbilical cord vein [52], placenta [49], chorionic plate [50], adipose [113], and skin [46] have shown the restoration of ovarian function in many reproductive disease models. Due to their low immunogenicity, migratory, and homing properties, MSCs have been widely used to restore ovarian functions in POF models.…”

Section: Direct Utilization Of Undifferentiated Stem Cells In Curing mentioning

confidence: 99%

“…Recently, researchers have used MSC-derived exosomes or microvesicles to evaluate their effect on diseased models [43][44][45]. In a chemotherapy-induced rat ovarian failure study, the transplantation of bone marrow MSCs (BMSCs)-derived exosomes exhibited an increase in the number of basal and sinus follicles, elevated levels of E2 and AMH and reduced levels of FSH and LH in the serum, and it also improved the estrus cycle in rat POF models [55]. The main reason behind these improvements was found to be episomal micro RNA, i.e., miR-144-5p derived from BMSCs exosomes.…”

Section: Direct Utilization Of Undifferentiated Stem Cells In Curing mentioning

confidence: 99%

“…However, due to the sophisticated isolation methods that are needed, confirmation criteria and very low cell yield, VSELs usage at large scale is limited and will need more time for proper exploration. Despite all these developments, the direct use of stem cells (undifferentiated state) have also revealed impressive results in treating disorders like POF and POI due to their low immunogenicity, paracrine signals and homing abilities [46][47][48][49][50][51][52][53][54][55][56]. Additionally, researchers throughout the world are putting in their best efforts to standardize differentiation protocols to get safer and more desirable results.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Bharti

Jang

Lee

et al. 2020

Cells

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In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.

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Section: Direct Utilization Of Undifferentiated Stem Cells In Curing mentioning

confidence: 99%

Section: Direct Utilization Of Undifferentiated Stem Cells In Curing mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Bharti

Jang

Lee

et al. 2020

Cells

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“…Exosomes are important vehicles for intercellular communication, and as such, are critical for many physiological functions. Recent studies indicated that exosomal miRNAs can regulate intercellular signal transduction and control molecular activities in different diseases [ 60 , 61 , 62 , 63 ]. Two studies have demonstrated a role of miRNAs carried by BMSCs-derived exosomes in promoting the recovery of ovarian function in a POF animal model [ 61 , 62 ].…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

Esfandyari

Chugh

Park

et al. 2020

Cells

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Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy, with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency, and to improve reproductive health for a significant number of women worldwide.

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“…Researchers have demonstrated that paracrine factors, including VEGF, HGF, IGF-1, and FGF2, mediate the repair of damaged ovaries [2,3]. Others have suggested that stem cell-derived exosomes and exosomal microRNAs (miR-144-5p) inhibit ovarian cell apoptosis [4][5][6]. Recently, several studies noted that material transfer between host and donor cells accounts for the rescue effect of stem cell therapy [7,8].…”

Section: Introductionmentioning

confidence: 99%

Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease

et al. 2020

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Background: Human amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application. Methods: Vitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTXdamaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function. Results: Our results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs.(Continued on next page) Conclusion: Treatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.

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Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN

Cited by 153 publications

References 42 publications

In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease

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