Feasibility investigation of allogeneic endometrial regenerative cells

Zhong, Zhaohui; Patel, Amit N.; Ichim, Thomas E.; Riordan, Neil H; Wang, Hao; Wei, Min; Woods, Erik J.; Reid, M M; Mansilla, Eduardo; Marín, Gustavo Horacio; Drago, Hugo; Murphy, Michael P.; Minev, Boris

doi:10.1186/1479-5876-7-15

Cited by 112 publications

(83 citation statements)

References 42 publications

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“…Furthermore, numerous preclinical studies have revealed that administration of MenSCs to injured tissues in situ or via intravenous injection induced structural restoration as well as functional improvements in heart failure (Bockeria et al 2013, Jiang et al 2013 and critical limb ischemia (Murphy et al 2008). The similar outcomes were observed in several clinical studies (Zhong et al 2009, Ichim et al 2010a. However, there was no report about MenSCs transplantation for the treatment of IUAs, which was an intractable gynecological disease in assisted reproductive technology.…”

Section: Discussionmentioning

confidence: 55%

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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Section: Discussionmentioning

confidence: 55%

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

et al. 2016

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“…Notwithstanding, the use of menstrual blood-derived stem cells for allogeneic transplantation may be an equally potential approach to cell therapy, along the line of investigations on therapeutic indications rendered by stem cells harvested from umbilical cord or bone marrow. Of note, menstrual bloodderived stem cells, referred to as endometrial regenerative cells (ERC), have been shown to be safe when transplanted intravenously and intrathecally in 4 patients with multiple sclerosis, characterized by absence of immunological reactions or treatment-associated adverse effects [68].…”

Section: Figmentioning

confidence: 99%

Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke

Borlongan

Kaneko

Maki

et al. 2010

Stem Cells and Development

187

174

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Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is fi nding the optimal cell type that will allow benefi t to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited signifi cantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also signifi cantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of "individually tailored" donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefi ts afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.

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“…Taking note of reports that TGF beta is normally fulfills a key function in regulating the cyclical nature of endometrial proliferative activity [7,35], that TGF beta is of fundamental importance in the cooperative interaction with the immune system in the management of angiogenesis in the endometrium [36], and also plays a major role in the repair of post-traumatic uterine tissue [3], we should recognize the relevance of the selected areas of research, both for theoretical medicine, as well as for implications in public health practice. The data obtained from the use of sodium chloride to stimulate production of TGF beta in the group of animals exposed to barium sulfate provide additional support for this conclusion.…”

Section: Discussionmentioning

confidence: 99%