Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Aupperle, H.; Garbade, Jens; Schubert, Andreas; Barten, M.J.; Dhein, Stefan; Schoon, H.-A.; Mohr, Friedrich–Wilhelm

doi:10.1354/vp.44-4-494

Cited by 26 publications

(20 citation statements)

References 35 publications

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“…Potentially, stem cells could alter collagenase activity or other enzymatic pathways responsible for pathologic heart wall thinning in injured myocardium, resulting in digestion of scar tissues and modification of extracellular matrix proteins [30]. Overexpression of collagen type I and III may protect infarcted myocardium from remodeling and dilation, but the increase in collagen synthesis in myocardium could result in stiffness and dysfunction of the damaged heart.…”

Section: Discussionmentioning

confidence: 99%

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

Mostafa¹,

Nematollahi-Mahani²,

Deilamy³

et al. 2011

Cardiology

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Objectives: Human umbilical cord mesenchymal cells (hUCM) can be easily obtained and processed in a laboratory. These cells may be considered as a suitable source in the repair of heart failure diseases. We, therefore, examined whether these cells may contribute to heart regeneration following an acute experimental myocardial infarction (MI). Methods: MI-induced animals received 5 × 10⁶ hUCM cells, 5 × 10⁶ 5-azacytidine-treated cells (dhUCM), or PBS alone, subepicardially. A group of animals with MI and no other former intervention served as controls. dhUCM cells were assessed for F-actin, myogenin and troponin-I expression. Results: dhUCM cells appeared as binucleated cells with extensive cytoplasmic processes. These differentiated cells were F-actin and myogenin positive. Thirty days after LAD ligation, left ventricular ejection fraction and the percentage of fractional shortening improved significantly in cell-receiving animals. In addition, the amount of scar tissue was significantly reduced in hUCM and dhUCM groups compared to MI group (p < 0.05). These parameters were comparable between hUCM and dhUCM groups. Histopathological evaluations revealed that some engrafted cells adjacent to and remote from the MI area expressed troponin-I, F-actin and connexin43. Conclusion: These findings demonstrated the potential therapeutic use of either differentiated or undifferentiated hUCM cells in treatment of heart failure conditions.

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Section: Discussionmentioning

confidence: 99%

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

Mostafa¹,

Nematollahi-Mahani²,

Deilamy³

et al. 2011

Cardiology

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“…VEGF treated animals have shown low fibrosis tissue compared with MI and PBS groups, but no significant difference was observed with the dhUCM group. Previous studies had indicated that VEGF declined scar tissue in infarcted heart [54,55]. A possible explanation for the way VEGF decreases fibrosis formation is: VEGF induces the migration of endothelial, CSC and aortic smooth muscle cells to the infarcted area, triggers angiogenesis and facilitates the survival of vessels, promotes the proliferation and migration of cardiomyocytes and prevents their deaths by apoptosis.…”

Section: Discussionmentioning

confidence: 98%

Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor

Moradi¹,

Abbasi²,

Farid³

et al. 2013

TOTERMJ

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Abstract:Objectives: In the previous study, although it has been shown that intramyocardial injection of human umbilical cord matrix stem cell (hUCM) improved cardiac function 4 weeks post MI, but angiogenesis has not been observed. Angiogenesis and replacing lost cardiomyocytes with new, live cardiomyocytes are considered as two key agents in cardiac repair. To achieve the above two factors we examined the effects of combination of stem cell and angiogenic therapy approaches by simultaneously injection of hUCM-derived cardiomyocytes with vascular endothelial growth factor (VEGF) in cardiac repair.Methods: MI-induced animals(by ligation of LAD) received 50 µl PBS, 5 × 10 6 differentiated hUCM cells (dhUCM), 5µg VEGF in normal saline and 5 × 10 6 dhUCM cells combined with 5µg VEGF in normal saline, intramyocardialy. MI group, with no other intervention, served as a control group. We were assessed survival, migration and integration of dhUCM cells, as well as angiogenesis eight weeks post MI induction.Results: Eight weeks post MI, although dhUCM and VEGF groups have shown that LVEF and LVFS improved significantly, but animals in dhUCM+VEGF group have the highest rise in LVEF and LVFS in comparison to the other MI-induced groups (p<0.05). Histological and morphological analysis have revealed that myocardium of animals in dhUCM+VEGF group have the highest vascular density and the lowest fibrosis tissue in comparison to the other MIinduced groups (p<0.05). Immunohistological assessments revealed that transplanted dhUCM cells have survived, migrated to infarcted area and integrated with recipient cardiac tissue. Conclusion:we have found that intramyocardial administration of dhUCM cells combined with VEGF improved cardiac function, enhanced angiogenesis and reduced fibrosis tissue formation after MI, eight weeks post MI.

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“…De modo semelhante, Ivanová et al (2012) também não encontraram formas inativas e/ou ativas da MMP9 no tecido cardíaco de ratos. Por outro lado, Aupperle et al (2007), por meio de imunoistoquímica, encontrou aumento na imunomarcação de MMP1, MMP2 e MMP9 em cardiomiócitos de coelhos com cardiomiopatia induzida por DOX, comparativamente aos animais do grupo Sham.…”

Section: Discussionunclassified

Ação do extrato etanólico da casca do pequi (Caryocar brasiliense) na cardiotoxicidade crônica induzida por doxorrubicina em ratos

et al. 2017

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ABSTRACT.-Moura L.R., Orpinelli S.R.T., Sousa J.H., Faleiro M.B.R., Conceição E. Goiânia, Doxorubicin (DOX) is a chemotherapic drug used in the treatment of malignancies, but has the cardiotoxicity as collateral effect. The objective of this study was to evaluate the action of pequi shell etanolic extract (Caryocar brasiliense) (PSEE) through morphological evaluation (macroscopic, microscopic and ultramicroscopic), and to evaluate the expression of metalloproteinases (MMP2 and MMP9) and its tissue inhibitors (TIMP1 and TIMP2) in the myocardium of rats with chronic cardiotoxicity by DOX and treated or not with PSEE. The experiment lasted three months and 30 Wistar rats were divided into six groups of five animals. G1 and G2 received 300mg/kg and 600mg/kg of PSEE, respectively, as pretreatment, by gavage for seven days and continued treatment for 21 days of application of DOX. In G1, G2, G3, G4 and GC, cardiotoxicity was induced with weekly applications of 2mg/kg DOX, intraperitoneally, totaling four applications (8 mg/kg), and in the Sham group (GS) 1ml of saline solution was applied. G3 animals received daily 300mg/ kg of PSEE, and G4, 600mg/kg, by gavage, for 21 days of application of DOX. The GC and GS received 1ml of water daily by gavage also. After the completion of the application, the animals were kept for two months, with three months of experiment. Macroscopic evaluation was performed after 90 days, at which time samples were taken for analysis in electron microscopy, histopathology and immunohistochemistry. At necropsy, ascites was observed in animals that received DOX. There was a low mortality rate (3.33%), being one mouse that developed false road pneumonia. There was no change in weights and measures of the rat hearts. At doses of 300 and 600mg/kg, the PSEE attenuates myocyte vacuolar degeneration. At a dose of 600mg/kg, PSEE reduces amount Anitschkow cells. There was no significant result on the immunostaining of MMP, but considering their inhibitors (TIMP) there was a greater immunostaining of TIMP2 in GC, the group that received only DOX. It was concluded that PSEE is effective in minimizing effects of chronic cardiotoxicity induced by DOX in the myocardium of rats, whereas at doses of 300 and 600mg/ 1 Recebido em 13 de abril de 2016.Aceito para publicação em 12 de setembro de 2016.

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Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model

Cited by 26 publications

References 35 publications

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor

Ação do extrato etanólico da casca do pequi (Caryocar brasiliense) na cardiotoxicidade crônica induzida por doxorrubicina em ratos

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