Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure

Lai, Dongmei; Wang, Fangyuan; Yao, Xiaofen; Zhang, Qiuwan; Wu, Xiaoxing; Xiang, Charlie

doi:10.1186/s12967-015-0516-y

Cited by 167 publications

(120 citation statements)

References 43 publications

(61 reference statements)

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“…We and other groups have reported the potential application of EnSCs to restore function of injured tissues91238. However, there are some concerns about the potential risk of MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…The noncontroversial extraction is also autologous and thus avoiding critical ethical issues9. A large number of reports have shown the therapeutic potential of EnSCs in restoring tissue function, such as treating myocardial infarction10, ameliorating stroke11, and improving chemotherapy-induced premature ovarian failure/insufficiency12. However, whether EnSCs endow intrinsic anti-tumor properties on cancer including epithelial ovarian cancer has never been reported before.…”

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confidence: 99%

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Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

Wang

Zhang

et al. 2016

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Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer.

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“…We and other groups have reported the potential application of EnSCs to restore function of injured tissues91238. However, there are some concerns about the potential risk of MSCs.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

Wang

Zhang

et al. 2016

Sci Rep

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“…MenSCs were isolated and provided by the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University (Mou et al 2013, Wu et al 2014, Lai et al 2015. Briefly, human menstrual blood was collected The χ 2 test was applied.…”

Section: Menscs Culture and Labelingmentioning

confidence: 99%

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

et al. 2016

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Intrauterine adhesions are common acquired endometrial syndromes secondary to endometrial injury, with limited effective therapies. Recently, several studies have reported that bone marrow stem cells (BMSCs) could repair injured endometrium in animal experiments. However, the role of stem cells in endometrial injury repair and its therapeutic mechanisms remain unclear. Here, we established mouse endometrial injury model and examined the benefit of human endometrial mesenchymal stem cells derived from menstrual blood (MenSCs) in restoration of injured endometrium. Injured endometrium exhibited significantly accelerated restoration at Day 7 after MenSCs transplantation, with increased endometrial thickness and microvessel density. Moreover, the fertility of mice with injured endometrium was improved, with higher conception rate (53.57% vs 14.29%, P = 0.014) and larger embryo number (3.1 ± 0.6 vs 0.9 ± 0.7, P = 0.030) in MenSCs group than control group, while no difference was found in undamaged horns between two groups. Conditioned medium from MenSCs (MenSCs-CM) could decrease H 2 O 2 -induced apoptosis of human umbilical vein endothelial cells (HUVECs) and promote proliferation, migration and angiogenesis. Angiogenesis effect of MenSCs-CM was also confirmed in Matrigel plug assay in mice. Furthermore, we discovered that MenSCs-CM could activate AKT and ERK pathways and induce the overexpression of eNOS, VEGFA, VEGFR1, VEGFR2 and TIE2 in HUVECs, which are critical in MenSCs-CM-induced angiogenesis. Angiogenesis induced by MenSCs-CM could be reversed by inhibitors of AKT and/or ERK. Taken together, we concluded that MenSCs could restore injured endometrium and improve the fertility of the endometrial injury mice, which was partially attributed to angiogenesis induced by MenSCs.Reproduction (2016) 152 389-402

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“…Exhaustion of the germinal stem cell reserve induced by chemotherapy was also decreased. 99 This evidence suggests a possible use of these cells as a cellular therapy for patients undergoing chemotherapy.…”

Section: Endometrium As a Source Of Mesenchymal Stem Cellsmentioning

confidence: 98%

The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

2017

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Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.

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Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure

Cited by 167 publications

References 43 publications

Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

Human endometrial mesenchymal stem cells exhibit intrinsic anti-tumor properties on human epithelial ovarian cancer cells

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways

The endometrium as a source of mesenchymal stem cells in domestic animals and possible applications in veterinary medicine

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