Stem Cell Therapy for Pediatric Dilated Cardiomyopathy

Selem, Sarah; Kaushal, Sunjay; Hare, Joshua M.

doi:10.1007/s11886-013-0369-z

Cited by 25 publications

(26 citation statements)

References 54 publications

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“…This can be achieved by modulating T cell proliferation as well as by regulating the type and quantity of T cell secretions. At present, MSCs provide a promising option (Selem et al, 2013) in the treatment of dilated cardiomyopathy. In rats with myocardial infarctions, it has been shown that the earlier the MSC transplantation was performed, the better the recovery of heart function was.…”

Section: Discussionmentioning

confidence: 99%

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Wang

Xiaojuan

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to observe the effect of Rehmannia glutinosa oligosaccharide (RGO) on differentiation of bone marrow mesenchymal stem cells (MSCs) into cardiomyocytelike cells . Rat MSCs were isolated, treated, and grouped as follows: RGO treatment group, 5-azacytidine (5-aza) treatment group, RGO + 5-aza treatment group, and control group. Following a four-week induction period, cardiac troponin I (cTnI) levels in MSCs were quantified by chemiluminescence, and the levels of myocardial enzymes creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB) were measured using a dry chemistry analyzer. The cTnIand connexin 43 (Cx43)-positive MSC population was identified by immunofluorescence, and expression levels of cTnI and Cx43 were analyzed by western blots. Following induction, cTnI, CK, and CK-MB levels were significantly higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups (P < 0.05). In addition, fluorescence intensity of cTnI and Cx43 was higher in the RGO + 5-aza group as compared with the RGO and 5-aza groups. No cTnI-or Cx43-positive cells were detected in the control group. Western blot analysis further confirmed that cTnI and Cx43 were not expressed in the control group, while cTnI and Cx43 was higher in the RGO + 5-aza group than in the RGO and 5-aza groups. These results suggest that MSCs can be induced by RGO to differentiate into cardiomyocyte-like cells in vitro, and that RGO in combination with 5-aza enhance differentiation of MSCs.

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Section: Discussionmentioning

confidence: 99%

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Wang

Xiaojuan

et al. 2016

Genet. Mol. Res.

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“…A well-studied type of stem cells consists of bone marrow-derived mesenchymal stem cells (MSCs), an undifferentiated population of cells capable of multipotent differentiation. Transplanted MSCs functionally recover acute and chronic ischemic myocardium in preclinical models of myocardial infarction, despite their limited engraftment in the injured myocardium (33). The precise mechanism of action has yet to be defined, but it may involve secretion of paracrine factors and stimulation of endogenous mechanisms of myocardial repair (3).…”

Section: We Demonstrate For the First Time That Intramyocardial Injecmentioning

confidence: 99%

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload

Wehman

Sharma

Pietris

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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(MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n ϭ 5) or placebo (n ϭ 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P Ͻ 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P Ͻ 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P Ͻ 0.0001), superior recruitment of endogenous c-kitϩ cardiac stem cells to the RV (P Ͻ 0.0001) and increased proliferation of cardiomyocytes (P ϭ 0.0009) and endothelial cells (P Ͻ 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P ϭ 0.008), increased cardiomyocyte cross-sectional area (P ϭ 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, ␤-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions. stem cell therapy; congenital heart disease; right ventricle; pressure overload CONGENITAL HEART DISEASE (CHD) is the leading cause of morbidity and mortality in children with birth defects. While surgical interventions have dramatically improved outcomes and longevity in patients with CHD, many patients still progress to heart failure, a population that has grown significantly over the last decade (30). In contrast to adult patients, in whom ischemic heart disease is the predominant etiology of heart failure, children with CHD are frequently exposed to acute or chronic ventricular pressure and volume overload, which if untreated can progress to ventricular dysfunction and ultimately to heart failure. Further, patients with CHD who develop right ventricular (RV) dysfunction have the poorest outcomes (23, 26), particularly in those patients with univentricular heart disease i...

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“…Among these 5 patients, 3 did not make it to the transplant. 60,61 Further studies are necessary to establish their role.…”

Section: E) New Therapiesmentioning

confidence: 99%

Dilated cardiomyopathy and severe heart failure. An update for pediatricians

Bottner¹,

Fernández²,

Valenzuela³

et al. 2018

Arch Argent Pediatr

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Dilated cardiomyopathy is the main cause of heart failure leading to heart transplant. Its prognosis is variable and depends on the etiology, the patient's age at onset, and the severity. The management of dilated cardiomyopathy is aimed at minimizing symptoms and preventing disease progression; it requires a comprehensive screening for comorbidities and the prevention of complications to improve the overall status of these children and mitigate their prognosis. Here we present a review oriented at the multidisciplinary management that pediatricians should consider when seeing these patients.

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Stem Cell Therapy for Pediatric Dilated Cardiomyopathy

Cited by 25 publications

References 54 publications

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload

Dilated cardiomyopathy and severe heart failure. An update for pediatricians

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