Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

Cao, Jian; Xiao, Li; Chang, Ning; Lei, Jing; Zhao, Dan; Gao, Kai; Jin, Zhengyu

doi:10.1016/j.jcyt.2015.05.003

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…However, in a previous publication, we used these same CM-mESC cells in non-infected CD1 mice immunosuppressed with cyclosporine and could also not detect a bioluminescent signal above background 8 days after cell injection [16], as shown in Figure 6. The limited survival of transplanted cells into the murine heart has been described by many authors irrespective of the use of syngeneic or allogeneic cells, of immunosuppressants and, of cell type [17,[26][27][28][29]. Thus, even though robust engraftment of human pluripotent stem cell-derived cardiomyocytes has been described in non-human primates [24,25] subject to myocardial infarction, we could not detect engraftment of CM-mESC in the murine CCC model.…”

Section: Discussioncontrasting

confidence: 56%

Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Brasil

Santos

Mendonça

et al. 2020

Cells

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Chagas disease discovered more than a century ago remains an incurable disease. The objective of this work was to investigate the therapeutic potential of cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a model of chronic Chagasic cardiomyopathy (CCC). Mouse embryonic stem cells (mESC) were characterized, transduced with luciferase, and submitted to cardiac differentiation. CM-mESC were labeled with superparamagnetic iron oxide particles. To induce CCC, mice were infected with Brazil strain trypomastigotes. At 150 days post-infection (dpi), infected animals were treated with CM-mESC or PBS. Cells were detected by magnetic resonance imaging (MRI) and bioluminescence. Cardiac function was evaluated by MRI and electrocardiogram at 150 and 196 dpi. CCC mice showed significant differences in MRI and ECG parameters compared to non-infected mice. However, no differences were observed in contractile and electrical parameters between cell and PBS injected groups, 45 days after cell transplantation. Cells were detected 24 h after transplantation by MRI. CM-mESC bioluminescence tracking demonstrated over 90% decrease in signal 8 days after treatment. Nevertheless, the Infected + CM-mESC group showed a significant reduction in the percentage of collagen fibers when compared to the Infected + PBS group. In conclusion, CM-mESC therapy was not effective in reversing cardiac functional changes induced by Chagas disease despite some improvement in myocardial fibrosis.

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Section: Discussioncontrasting

confidence: 56%

Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Brasil

Santos

Mendonça

et al. 2020

Cells

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“…Then, we analyzed the effects of the BEV delivery method on tumor growth by in vivo bioluminescence imaging – a noninvasive laboratory and clinical imaging technique at the molecular level that can monitor the localization, proliferation, migration, and differentiation of cells in vivo. 17 Herein, we found that luciferase activity in IT BEV-treated groups were much lower than that in the IV BEV-treated and untreated groups, which proved that IT BEV treatment at a lower dose could inhibit tumor growth more efficiently than the IV BEV method. To further confirm the outcome of BLI, the brains of mice in different groups were isolated at Day 28 after BEV treatment.…”

Section: Discussionmentioning

confidence: 70%

Delivery of bevacizumab by intracranial injection: assessment in glioma model

Liu¹,

Liu²,

Zhang³

et al. 2018

OTT

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BackgroundMany reports have indicated that the intravenous administration of bevacizumab produces a number of systemic side effects. Therefore, we investigated the therapeutic effects of intratumoral bevacizumab administration using a glioma animal model.MethodsThe glioma cell lines U251 and U87 that carried luciferase were implanted into the brains of mice to develop glioma models. Glioma-bearing mice were treated with bevacizumab intravenously or intratumorally by Alzet micro-osmotic pumps, and the survival time of mice was monitored. Tumor volumes and location were observed by fluorescence imaging and histological analysis. Levels of microvessel marker, cancer stem cell marker as well as angiogenesis-, invasion-, and inflammation-related factors in tumors were examined by immunohistochemical staining.ResultsMice treated with intratumoral low-dose bevacizumab had smaller tumor volumes, longer survival time, lower microvessel density, and fewer cancer stem cells as compared with untreated and intravenously treated mice. Furthermore, expression levels of inflammation-related factors increased signifiwhereas that of angiogenesis- and invasion-related factors decreased in intratumorally treated animals, compared with intravenously treated mice.ConclusionThese results implied bevacizumab delivery by intratumoral injection via Alzet micro-osmotic pumps may be a more effective and safer protocol for treating gliomas.

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“…Using adult multipotent cells, Cao et al [ 43 ] have shown that bone marrow mesenchymal cells remained for up to 6 days in the heart region when cells were transplanted in infarcted rats. In addition, Passipieri et al [ 12 ] detected placental-derived mesenchymal stem cells in the thoracic region of infarcted rats for 3 days after transplantation, despite using immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 99%

Embryonic stem cell-derived cardiomyocytes for the treatment of doxorubicin-induced cardiomyopathy

et al. 2018

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BackgroundDoxorubicin (Dox) is a chemotherapy drug with limited application due to cardiotoxicity that may progress to heart failure. This study aims to evaluate the role of cardiomyocytes derived from mouse embryonic stem cells (CM-mESCs) in the treatment of Dox-induced cardiomyopathy (DIC) in mice.MethodsThe mouse embryonic stem cell (mESC) line E14TG2A was characterized by karyotype analysis, gene expression using RT-PCR and immunofluorescence. Cells were transduced with luciferase 2 and submitted to cardiac differentiation. Total conditioned medium (TCM) from the CM-mESCs was collected for proteomic analysis. To establish DIC in CD1 mice, Dox (7.5 mg/kg) was administered once a week for 3 weeks, resulting in a cumulative Dox dose of 22.5 mg/kg. At the fourth week, a group of animals was injected intramyocardially with CM-mESCs (8 × 105 cells). Cells were tracked by a bioluminescence assay, and the body weight, echocardiogram, electrocardiogram and number of apoptotic cardiomyocytes were evaluated.ResultsmESCs exhibited a normal karyotype and expressed pluripotent markers. Proteomic analysis of TCM showed proteins related to the negative regulation of cell death. CM-mESCs presented ventricular action potential characteristics. Mice that received Dox developed heart failure and showed significant differences in body weight, ejection fraction (EF), end-systolic volume (ESV), stroke volume (SV), heart rate and QT and corrected QT (QTc) intervals when compared to the control group. After cell or placebo injection, the Dox + CM-mESC group showed significant increases in EF and SV when compared to the Dox + placebo group. Reduction in ESV and QT and QTc intervals in Dox + CM-mESC-treated mice was observed at 5 or 30 days after cell treatment. Cells were detected up to 11 days after injection. The Dox + CM-mESC group showed a significant reduction in the percentage of apoptotic cardiomyocytes in the hearts of mice when compared to the Dox + placebo group.ConclusionsCM-mESC transplantation improves cardiac function in mice with DIC.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0788-2) contains supplementary material, which is available to authorized users.

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Dual-modular molecular imaging to trace transplanted bone mesenchymal stromal cells in an acute myocardial infarction model

Cited by 6 publications

References 20 publications

Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Delivery of bevacizumab by intracranial injection: assessment in glioma model

Embryonic stem cell-derived cardiomyocytes for the treatment of doxorubicin-induced cardiomyopathy

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