Patel AN, Geffner L, Vina RF, et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg 2005;130:1631-8

Baylor University, Waco, Texas, United States
The Journal of thoracic and cardiovascular surgery (Impact Factor: 4.17). 12/2005; 130(6):1631-8. DOI: 10.1016/j.jtcvs.2005.07.056
Source: PubMed


Autologous adult stem cell transplantation has been touted as the latest tool in regenerative medical therapy. Its potential for use in cardiovascular disease has only recently been recognized. A randomized study was conducted with a novel epicardial technique to deploy stem cells as an adjuvant to conventional revascularization therapy in patients with congestive heart failure.
After institutional review board and government approval, adult autologous stem cell transplantation (CD34+) was performed in patients with ischemic cardiomyopathy and an ejection fraction of less than 35% who were scheduled for primary off-pump coronary artery bypass grafting. Preoperatively, the patients underwent echocardiography, stress thallium imaging single photon emission computed tomography, and cardiac catheterization to identify ischemic regions of the heart and to guide in the selection of stem cell injection sites. The patients were prospectively randomized before the operative therapy was performed. Patient follow-up was 1, 3, and 6 months with echocardiography, single photon emission computed tomography, and angiography.
There were 20 patients enrolled in the study. Ten patients had successful subepicardial transplantation of autologous stem cells into ischemic myocardium. The other 10 patients, the control group, only had off-pump coronary artery bypass grafting. There were 8 male and 2 female subjects in each group. The median number of grafts performed was 1 in both groups. On angiographic follow-up, all grafts were patent at 6 months. The ejection fractions of the off-pump coronary artery bypass grafting group versus the off-pump coronary artery bypass grafting plus stem cell transplantation group were as follows: preoperative, 30.7% +/- 2.5% versus 29.4% +/- 3.6%; 1 month, 36.4% +/- 2.6% versus 42.1% +/- 3.5%; 3 months, 36.5% +/- 3.0% versus 45.5% +/- 2.2%; and 6 months, 37.2% +/- 3.4% versus 46.1% +/- 1.9% (P < .001). There were no perioperative arrhythmias or neurologic or ischemic myocardial events in either group.
Autologous stem cell transplantation led to significant improvement in cardiac function in patients undergoing off-pump coronary artery bypass grafting for ischemic cardiomyopathy. Further investigation is required to quantify the optimal timing and specific cellular effects of the therapy.

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    • "The location can be identified preoperatively using imaging modalities, during surgery, by empirical observation.31) Direct intramyocardial injection can typically be conducted either during open heart surgery like coronary artery bypass graft32) or as a separate procedure performed without cardiac arrest via a lateral minithoracotomy.33) It offers the distinct advantage of targeting localized myocardium without perturbing any surrounding tissue and vasculature. "
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    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.
    Korean Circulation Journal 08/2013; 43(8):511-518. DOI:10.4070/kcj.2013.43.8.511 · 0.75 Impact Factor
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    • "The promising results of these pilot studies led to formal trials, which demonstrated statistically significant, albeit small, improvements in cardiac function. For example, a meta-analysis of 4 randomized controlled studies [6-9] and 2 cohort studies [10,11] evaluating autologous bone marrow cells administered transepicardially during coronary artery bypass graft (CABG) revealed a 5.4% increase in left ventricular ejection fraction (LVEF) in a total of 179 patients [12]. Bone marrow cells administered via the intracoronary route were analyzed in 8 clinical trials in post-infarct patients [13-22]. "
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    ABSTRACT: Heart failure is one of the key causes of morbidity and mortality world-wide. The recent findings that regeneration is possible in the heart have made stem cell therapeutics the Holy Grail of modern cardiovascular medicine. The success of cardiac regenerative therapies hinges on the combination of an effective allogeneic “off the shelf” cell product with a practical delivery system. In 2007 Medistem discovered the Endometrial Regenerative Cell (ERC), a new mesenchymal-like stem cell. Medistem and subsequently independent groups have demonstrated that ERC are superior to bone marrow mesenchymal stem cells (MSC), the most widely used stem cell source in development. ERC possess robust expansion capability (one donor can generate 20,000 patients doses), key growth factor production and high levels of angiogenic activity. ERC have been published in the peer reviewed literature to be significantly more effect at treating animal models of heart failure (Hida et al. Stem Cells 2008). Current methods of delivering stem cells into the heart suffer several limitations in addition to poor delivery efficiency. Surgical methods are highly invasive, and the classical catheter based techniques are limited by need for sophisticated cardiac mapping systems and risk of myocardial perforation. Medistem together with Dr. Amit Patel Director of Clinical Regenerative Medicine at University of Utah have developed a novel minimally invasive delivery method that has been demonstrated safe and effective for delivery of stem cells (Tuma et al. J Transl Med 2012). Medistem is evaluating the combination of ERC, together with our retrograde delivery procedure in a 60 heart failure patient, double blind, placebo controlled phase II trial. To date 17 patients have been dosed and preliminary analysis by the Data Safety Monitoring Board has allowed for trial continuation. The combined use of a novel “off the shelf” cell together with a minimally invasive 30 minute delivery method provides a potentially paradigm-shifting approach to cardiac regenerative therapy.
    Journal of Translational Medicine 03/2013; 11(1):56. DOI:10.1186/1479-5876-11-56 · 3.93 Impact Factor
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    • "Traditionally, cells intended for human use have been limited to those that can be isolated in large quantities. As a result, bone marrow mononuclear cells have become popular in clinical studies (Assmus et al., 2006; Diederichsen et al., 2008; Hamano et al., 2001; Lunde et al., 2006; Patel et al., 2005; Perin et al., 2003; Schachinger et al., 2004; Tse et al., 2003; Wollert et al., 2004). The use of this heterogeneous population of cells imparts difficulties in trying to assess which cell types within the mix contribute to improved function. "
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    ABSTRACT: Human mesenchymal stem cells (hMSC) have proven beneficial in the repair and preservation of infarcted myocardium. Unfortunately, MSCs represent a small portion of the bone marrow and require ex vivo expansion. To further advance the clinical usefulness of cellular cardiomyoplasty, derivation of "MSC-like" cells that can be made available "off-the-shelf" are desirable. Recently, human embryonic stem cell-derived mesenchymal cells (hESC-MC) were described. We investigated the efficacy of hESC-MC for cardiac repair after myocardial infarction (MI) compared to hMSC. Because of increased efficacy of cell delivery, cells were embedded into collagen patches and delivered to infarcted myocardium. Culture of hMSC and hESC-MCs in collagen patches did not induce differentiation or significant loss in viability. Transplantation of hMSC and hES-MC patches onto infarcted myocardium of athymic nude rats prevented adverse changes in infarct wall thickness and fractional area change compared to a non-viable patch control. Hemodynamic assessment showed that hMSCs and hES-MC patch application improved end diastolic pressure equivalently. There were no changes in systolic function. hES-MC and hMSC construct application enhanced neovessel formation compared to a non-viable control, and each cell type had similar efficacy in stimulating endothelial cell growth in vitro. In summary, the use of hES-MC provides similar efficacy for cellular cardiomyoplasty as compared to hMSC and may be considered a suitable alternative for cell therapy.
    Biotechnology and Bioengineering 01/2012; 109(1):274-83. DOI:10.1002/bit.23301 · 4.13 Impact Factor
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