Korean Circ J.  2013 Aug;43(8):511-518. 10.4070/kcj.2013.43.8.511.

The Role of Large Animal Studies in Cardiac Regenerative Therapy Concise Review of Translational Stem Cell Research

• Kwon SU
• Yeung AC
• Ikeno F

• KMID: 2224840
• DOI: http://doi.org/10.4070/kcj.2013.43.8.511

Abstract

Animal models have long been developed for cardiovascular research. These animal models have been helpful in understanding disease, discovering potential therapeutics, and predicting efficacy. Despite many efforts, however, translational study has been underestimated. Recently, investigations have identified stem cell treatment as a potentially promising cell therapy for regenerative medicine, largely because of the stem cell's ability to differentiate into many functional cell types. Stem cells promise a new era of cell-based therapy for salvaging the heart. However, stem cells have the potential risk of tumor formation. These properties of stem cells are considered a major concern over the efficacy of cell therapy. The translational/preclinical study of stem cells is essential but only at the beginning stages. What types of heart disease are indicated for stem cell therapy, what type of stem cell, what type of animal model, how do we deliver stem cells, and how do we improve heart function? These may be the key issues that the settlement of which would facilitate the transition of stem cell research from bench to bedside. In this review article, we discuss state-of-the-art technology in stem cell therapies for cardiovascular diseases.

Keyword

Translational research; Clinical trial; Stem cells; Heart diseases; Regenerative medicine

MeSH Terms

Animals
Cardiovascular Diseases
Heart
Heart Diseases
Models, Animal
Regenerative Medicine
Stem Cell Research
Stem Cells
Tissue Therapy
Translational Medical Research

Figure

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  Fig. 1 Potential mechanisms through which cell therapy contributes to cardiovascular repair. Cell therapy may contribute to cardiac and vascular repair depending on the target population.42) EC: endothelial cell, SMC: smooth muscle cell, CSC: cardiac stem cell.

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  Fig. 2 Swine myocardial infarction model using balloon occlusion. A: swine placed dorsally recumbent under biplane angiography. Vascular access is shown through the right carotid artery and the right external jugular vein. B: left coronary angiogram shows the LAD (arrow 1), left circumflex coronary artery (arrow 2), and the first diagonal branch of the LAD (arrow 3). C: balloon obstructing all distal flows of the LAD past the first diagonal (arrow 4). D: representative electrocardiographic changes during myocardial infarction.43) LAD: left anterior descending artery.

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  Fig. 3 Potential delivery routes for stem cells. Delivery options for implementing myocardial stem cell transfer. A: epicardial, B: endocardial, C: intracoronary, D: retroperfusion.

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  Fig. 4 Devices of transendocardial injection. A: the helical needle catheter is advanced through the Morph Universal Guide Catheter. Cells are injected through the helical tip. A second lumen at the base of the helix is used for contrast injection.39) B: injection catheter advanced into the left ventricle through the aortic valve. The catheter tip is placed against the endocardial surface (insert) with the needle extended into the myocardium, delivering stem cells. C: the NOGA Myostar Injection Catheter (Biosense Webster). D: NOGA 3D mapping.44)

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  Fig. 5 Global status and trends of stem cell clinical trials. A: currently, 236 clinical trials have been conducting (data from clinicaltrials.gov). B: according to different types of stem cells, clinical trials have been conducted from 1991 to 2010.45)

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