The Real Estate of Myoblast Cardiac Transplantation: Negative Remodeling Is Associated With Location

McCue, Jonathan D.; Swingen, Cory; Feldberg, Tanya; Caron, G; Kolb, Adam; Denucci, Christopher; Prabhu, Somnath J.; Motilall, Randy; Breviu, Brian; Taylor, Doris A.

doi:10.1016/j.healun.2007.10.011

Cited by 19 publications

(18 citation statements)

References 31 publications

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“…Extensive and indepth experimental efforts from various research groups have assessed the performance of skeletal myoblasts for the treatment of both ischemic and nonischemic cardiomyopathies both in small mouse [32], rat [28,45], rabbit [46,47], large sheep [40,48], dog [49,50] and pig [22,51–53] models. These studies have demonstrated that skeletal myoblasts effectively prevented left ventricular remodeling and preserved global parameters (ejection fraction and left ventricular pressure) as well as regional parameters (regional stroke work at the infarct site, wall thickness and myocardial tissue velocities) of myocardial contractility.…”

Section: Experimental Animal Studies Using Skeletal Myoblasts For Myomentioning

confidence: 99%

“…These studies have demonstrated that skeletal myoblasts effectively prevented left ventricular remodeling and preserved global parameters (ejection fraction and left ventricular pressure) as well as regional parameters (regional stroke work at the infarct site, wall thickness and myocardial tissue velocities) of myocardial contractility. The diastolic properties also demonstrated improvement with increased compliance of the infarcted myocardium [47,54]. …”

Section: Experimental Animal Studies Using Skeletal Myoblasts For Myomentioning

confidence: 99%

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Skeletal Myoblasts for Cardiac Repair

et al. 2010

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Stem cells provide an alternative curative intervention for the infarcted heart by compensating for the cardiomyocyte loss subsequent to myocardial injury. The presence of resident stem and progenitor cell populations in the heart, and nuclear reprogramming of somatic cells with genetic induction of pluripotency markers are the emerging new developments in stem cell-based regenerative medicine. However, until safety and feasibility of these cells are established by extensive experimentation in in vitro and in vivo experimental models, skeletal muscle-derived myoblasts, and bone marrow cells remain the most well-studied donor cell types for myocardial regeneration and repair. This article provides a critical review of skeletal myoblasts as donor cells for transplantation in the light of published experimental and clinical data, and indepth discussion of the advantages and disadvantages of skeletal myoblast-based therapeutic intervention for augmentation of myocardial function in the infarcted heart. Furthermore, strategies to overcome the problems of arrhythmogenicity and failure of the transplanted skeletal myoblasts to integrate with the host cardiomyocytes are discussed. Keywordsheart; myoblast; myocardium; stem cell Despite the advances in medical and surgical treatment of myocardial infarction, ischemic heart disease remains the leading cause of morbidity and mortality on a global scale [1]. The gravity of the problem can be assessed by the fact that mortality from ischemic heart disease exceeds the mortality from cancer -as the 1-year survival rate is lower than 50%. The immune and inflammatory responses following myocardial infarction are characterized by neutrophil and macrophage accumulation, cytokine secretion, recruitment of T and B cells, and formation of antibodies specific to myosin and actin [2]. The successive biochemical, structural and functional adaptive changes in the infarcted and hibernating myocardium lead to expansion of the infarction zone and scarring, while the hibernating myocardium in the periphery of the infarct become hypertrophic. The hearts of patients who survive the acute phase of myocardial infarction subsequently enter into a vicious cycle of left ventricular remodeling as part of the compensatory mechanism caused by the massive loss of functioning cardiomyocytes. Various therapeutic options including pharmacotherapeutic intervention (e.g., angiotensin-converting enzyme inhibitors, β-blockers, diuretics and angiotensin receptors blockers) are available but only provide a symptomatic relief without † Author for correspondence: Tel.: +1 513 558 0145, haiderkh@ucmail.uc.edu. Financial & competing interests disclosureThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. addressing the fundamental issue of myoc...

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Section: Experimental Animal Studies Using Skeletal Myoblasts For Myomentioning

confidence: 99%

Section: Experimental Animal Studies Using Skeletal Myoblasts For Myomentioning

confidence: 99%

Skeletal Myoblasts for Cardiac Repair

et al. 2010

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“…85 In a rabbit MI model, injection of SkM in the infarct border zone led to erratic ventricular ectopy, 86 and injection of SkMs in the scar center elicited negative LV remodeling and late ventricular ectopies. 87 Intramyocardial injection of bone marrow mononuclear cells (BMMNCs) in a rat chronic heart failure model 88 also generated cell clusters in the infarct border zone, which most likely were responsible for the increased ventricular arrhythmias. Myocardial injection per se may also lead to scarring.…”

Section: Future Electrophysiological Challenges In Cardiomyogenesismentioning

confidence: 99%

Electrophysiological Challenges of Cell-Based Myocardial Repair

2009

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“…For this reason, it is important to deliver the maximum available cells. The technical approach used to implant the cells could influence the efficacy of cellular CMP [33,34]. In fact, cell mortality after transplantation appears to be more important when grafted in the center of highly fibrotic ischemic scars (decreased oxygen and nutrient supply to the chronic ischemic myocardium).…”

Section: Cell Deliverymentioning

confidence: 99%

Cellular cardiac regenerative therapy in which patients?

Chachques¹

2009

Expert Review of Cardiovascular Therapy

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Cell-based myocardial regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles owing to ischemic and nonischemic myocardial diseases. A variety of myogenic and angiogenic cell types have been proposed, such as skeletal myoblasts, mononuclear and mesenchymal bone marrow cells, circulating blood-derived progenitors, adipose-derived stromal cells, induced pluripotent stem cells, umbilical cord cells, endometrial mesenchymal stem cells, adult testis pluripotent stem cells and embryonic cells. Current indications for stem cell therapy concern patients who have had a left- or right-ventricular infarction or idiopathic dilated cardiomyopathies. Other indications and potential applications include patients with diabetic cardiomyopathy, Chagas heart disease (American trypanosomiasis), ischemic mitral regurgitation, left ventricular noncompacted myocardium and pediatric cardiomyopathy. Suitable sources of cells for cardiac implant will depend on the types of diseases to be treated. For acute myocardial infarction, a cell that reduces myocardial necrosis and augments vascular blood flow will be desirable. For heart failure, cells that replace or promote myogenesis, reverse apoptopic mechanisms and reactivate dormant cell processes will be useful. It is important to note that stem cells are not an alternative to heart transplantation; selected patients should be in an early stage of heart failure as the goal of this regenerative approach is to avoid or delay organ transplantation. Since the cell niche provides crucial support needed for stem cell maintenance, the most interesting and realistic perspectives include the association of intramyocardial cell transplantation with tissue-engineered scaffolds and multisite cardiac pacing in order to transform a passive regenerative approach into a 'dynamic cellular support', a promising method for the creation of 'bioartificial myocardium'.

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The Real Estate of Myoblast Cardiac Transplantation: Negative Remodeling Is Associated With Location

Cited by 19 publications

References 31 publications

Skeletal Myoblasts for Cardiac Repair

Skeletal Myoblasts for Cardiac Repair

Electrophysiological Challenges of Cell-Based Myocardial Repair

Cellular cardiac regenerative therapy in which patients?

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