Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model

Qi, Chun Mei; Ma, Gen Shan; Liu, Nai Feng; Shen, Cheng; Chen, Zhong; Liu, Xiao Jun; Hu, Yao; Zhang, Xiao Li; Teng, Gao Jun; Ju, Sheng Hong; Ma, Ming; Tang, Yao

doi:10.1097/00029330-200803020-00016

Cited by 27 publications

(13 citation statements)

References 27 publications

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“…Other studies have reported decreased MI expansion in pig and sheep MI models with mesenchymal stem cells delivered into the myocardium within 72 hours of MI56,57,62and attenuation of EF deterioration with delivery one month post-MI 58,63. Alternatively, intracoronary59,60 and systemic61 delivery of mesenchymal stem cells have also been examined, further exemplifying the utility of large animal models in clarifying variables in stem cell therapies. It is likely that these translational studies in large animal models will be necessary if the tremendous potential suggested by rodent studies is to be realized clinically.…”

Section: Developing New Therapeutic Targets In Hfmentioning

confidence: 99%

Large Animal Models of Heart Failure

Dixon

Spinale

2009

Circ: Heart Failure

261

125

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Abstract-Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, that continues to be highly prevalent and morbid. Because of the growing burden of HF as the population ages, the need to develop new pharmacological treatments and therapeutic interventions is of paramount importance. Key Words: myocardial infarction Ⅲ myocardial remodeling Ⅲ overload states Ⅲ rapid pacing C ongestive heart failure (HF) is a constellation of symptoms, with hallmarks of fatigue and dyspnea, which continues to be a highly prevalent and morbid clinical syndrome. Although the etiologic underpinnings of HF can be diverse, common pathophysiologic features include changes in left ventricle (LV) structure, function, and neurohormonal activation. The impact of HF will undoubtedly become even more substantial as the population ages. Accordingly, the need to develop new pharmacological treatments and therapeutic interventions for HF is of paramount importance. The journey from discovery, to understanding, to clinical application of the biological basis of HF is one that can only be traveled with the use of large animal models that recapitulate this clinical phenotype.The current pharmacological armamentarium in the treatment of HF includes angiotensin-converting enzyme inhibitors, aldosterone antagonists, and angiotensin and ␤-adrenergic receptor blockade. 1 Although inhibition of the renin-angiotensin-aldosterone and sympathetic adrenergic systems have provided clear benefit to those suffering from HF, the disease process nonetheless continues. Therefore, further research is required to find additional pathways and mechanisms to target in the battle against HF. The Need for Large Animal Models of HFSignificant insight into the molecular and cellular basis of cardiovascular biology has come from small animal models, particularly mice. However, significant differences exist with regard to cardiac characteristics such as heart rate, oxygen consumption, adrenergic receptor ratios, and response to loss of regulatory proteins, when mice are contrasted to humans. 2,3 Moreover, contractile protein expression, critical to the excitation-contraction coupling process, seems to differ between the 2 species, as evidenced by their differing predominant myosin isoforms. 2 Finally, evidence exists of significant phenotypic differences between mouse and human stem cells. 3 Consequently, extrapolation of murine systems, particularly after induction of cardiovascular stress, becomes problematic when making interpretations of human HF pathophysiology. Therefore, large animal models of HF, which more closely approximate human physiology, function, and anatomy, are essential to develop the discoveries from murine models into clinical therapies and interventions for HF.This review aims to summarize some of the more frequently used large animal models, which recapitulate the clinical HF phenotype arising from the common clinical etiologies of myocardial ischemia/infarction, ventricular overload states, and dilated cardiomyopath...

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Section: Developing New Therapeutic Targets In Hfmentioning

confidence: 99%

Large Animal Models of Heart Failure

Dixon

Spinale

2009

Circ: Heart Failure

261

125

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“…However, the presence of homing signals and the antifibrotic milieu may be of benefit. Another study 134 where MSCs were intracoronarily infused into porcine heart 5 days after infarction, showed improvement in EF and scar reduction in MSC treated animals. In another study 135 , where different doses of MSCs were used three days after MI, there was no dose dependent effect on scar size reduction or EF improvement 12 weeks post transplantation.…”

Section: Introductionmentioning

confidence: 99%

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

Karantalis

Hare

2015

Circulation Research

372

332

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Despite substantial clinical advances over the past 65 years, cardiovascular disease remains the leading cause of death in America. The past 15 years has witnessed major basic and translational interest in the use of stem and/or precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells (MSCs) are widely studied and in early stage clinical studies show promise for repair and regeneration of cardiac tissues. The ability of MSCs to differentiate into mesoderm and non-mesoderm derived tissues, their immunomodulatory effects, their availability and their key role in maintaining and replenishing endogenous stem cell niches have rendered them one of the most heavily investigated and clinically tested type of stem cell. Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. Here, we review the biology of MSCs, their interaction with endogenous molecular and cellular pathways, and their modulation of immune responses. Additionally, we discuss factors that enhance their proliferative and regenerative ability and factors that may hinder their effectiveness in the clinical setting.

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“…Also, the conventional over-the-wire balloon angioplasty catheters can be used for injection of the cells (Wang et al, 2009). In a swine model of AMI, intracoronary delivery of MSCs resulted in decreased scar size and improved EF (Qi et al, 2008). Similarly, an earlier clinical trial of 69 patients receiving intracoronary MSCs following AMI resulted in an improvement in LVEF (Chen et al, 2004).…”

Section: The Preclinical and Clinical Studies Of Different Exogenous mentioning

confidence: 99%

Translational Findings From Cardiovascular Stem Cell Research

Mazhari

Hare

2012

Trends in Cardiovascular Medicine

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The possibility of using stem cells to regenerate damaged myocardium has been actively investigated since the late 1990s. Consistent with the traditional view that the heart is a “post-mitotic” organ that possesses minimal capacity for self-repair, much of the preclinical and clinical work has focused exclusively on introducing stem cells into the heart, with the hope of differentiation of these cells into functioning cardiomyocytes. This approach is ongoing and retains promise but to date has yielded inconsistent successes. More recently, it has become widely appreciated that the heart possesses endogenous repair mechanisms that, if adequately stimulated, might regenerate damaged cardiac tissue from in situ cardiac stem cells. Accordingly, much recent work has focused on engaging and enhancing endogenous cardiac repair mechanisms. This article reviews the literature on stem-cell based myocardial regeneration, placing emphasis on the mutually enriching interaction between basic and clinical research.

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Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model

Cited by 27 publications

References 27 publications

Large Animal Models of Heart Failure

Large Animal Models of Heart Failure

Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease

Translational Findings From Cardiovascular Stem Cell Research

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