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Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats.

ABSTRACT: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of osteoclasts were downregulated in OVX-MSCs. Moreover, therapeutic effects of OVX-MSCs were decreased in OVX rats. Accordingly, we developed a new activator for BM-MSCs using human umbilical cord extracts, Wharton's jelly extract supernatant (WJS), which improved cell proliferation, mobilisation and suppressive effects on activated osteoclasts in OVX-MSCs. Bone volume, RANK and TRACP expression of osteoclasts, as well as proinflammatory cytokine expression in bone tissues, were ameliorated by OVX-MSCs activated with WJS (OVX-MSCs-WJ) in OVX rats. Fusion and bone resorption activity of osteoclasts were suppressed in macrophage-induced and primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast-specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX-MSCs-WJ in vitro. In this study, we developed a new activator, WJS, which improved the functional abnormalities and therapeutic effects of BM-MSCs on postmenopausal osteoporosis.

SUBMITTER: Saito A

PROVIDER: S-EPMC5773568 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats.

Saito Akira A Nagaishi Kanna K Iba Kousuke K Mizue Yuka Y Chikenji Takako T Otani Miho M Nakano Masako M Oyama Kazusa K Yamashita Toshihiko T Fujimiya Mineko M

Scientific reports 20180118 1

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell p ...[more]

PMID: 29348535

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Project description:ObjectiveUmbilical cord abnormalities are commonly cited as a cause of stillbirth, but details regarding these stillbirths are rare. Our objective was to characterize stillbirths associated with umbilical cord abnormalities using rigorous criteria and to examine associated risk factors.MethodsThe Stillbirth Collaborative Research Network conducted a case-control study of stillbirth and live births from 2006 to 2008. We analyzed stillbirths that underwent complete fetal and placental evaluations and cause of death analysis using the INCODE (Initial Causes of Fetal Death) classification system. Umbilical cord abnormality was defined as cord entrapment (defined as nuchal, body, shoulder cord accompanied by evidence of cord occlusion on pathologic examination); knots, torsions, or strictures with thrombi, or other obstruction by pathologic examination; cord prolapse; vasa previa; and compromised fetal microcirculation, which is defined as a histopathologic finding that represents objective evidence of vascular obstruction and can be used to indirectly confirm umbilical cord abnormalities when suspected as a cause for stillbirth. We compared demographic and clinical factors between women with stillbirths associated with umbilical cord abnormalities and those associated with other causes, as well as with live births. Secondarily, we analyzed the subset of pregnancies with a low umbilical cord index.ResultsOf 496 stillbirths with complete cause of death analysis by INCODE, 94 (19%, 95% CI 16-23%) were associated with umbilical cord abnormality. Forty-five (48%) had compromised fetal microcirculation, 27 (29%) had cord entrapment, 26 (27%) knots, torsions, or stricture, and five (5%) had cord prolapse. No cases of vasa previa occurred. With few exceptions, maternal characteristics were similar between umbilical cord abnormality stillbirths and non-umbilical cord abnormality stillbirths and between umbilical cord abnormality stillbirths and live births, including among a subanalysis of those with hypo-coiled umbilical cords.ConclusionUmbilical cord abnormalities are an important risk factor for stillbirth, accounting for 19% of cases, even when using rigorous criteria. Few specific maternal and clinical characteristics were associated with risk.

Project description:Human umbilical cord mesenchymal stem cells (hUCMSC) have shown promising potential in ameliorating brain injury, but the mechanism is unclear. We explore the role of NogoA/NgR/Rho pathway in mediating hUCMSC to improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP (cerebral palsy) rat model in order to promote the clinical application of stem cell therapy in CP. The injury model of HT22 cells was established after 3 h hypoxia, and then co-cultured with hUCMSC. The rat model of CP was established by ligation of the left common carotid artery for 2.5 h. Subsequently, hUCMSC was administered via the tail vein once a week for a total of four times. The neurobehavioral status of CP rats was determined by behavioral experiment, and the pathological brain injury was determined by pathological staining method. The mRNA and protein expressions of NogoA, NgR, RhoA, Rac1, and CDC42 in brain tissues of rats in all groups and cell groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence. The CP rats exhibited obvious motor function abnormalities and pathological damage. Compared with the control group, hUCMSC transplantation could significantly improve the neurobehavioral situation and attenuate brain pathological injury in CP rats. The relative expression of NogoA, NgR, RhoA mRNA, and protein in brain tissues of rats in the CP group was significantly higher than the rats in the sham and CP+hUCMSC group. The relative expression of Rac1, CDC42 mRNA, and protein in brain tissues of rats in the CP group was significantly lower than the rats in the sham and CP+hUCMSC group. The animal experiment results were consistent with the experimental trend of hypoxic injury of HT22 cells. This study confirmed that hUCMSC can efficiently improve neurobehavioral status and alleviate brain injury in hypoxia/ischemia-induced CP rat model and HT22 cell model through downregulating the NogoA/NgR/Rho pathway.

Dataset Information

Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats.

Publications

Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats.

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