Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)

Tse, Hung‐Fat; Thambar, S.; Kwong, Yok–Lam; Rowlings, Philip; Bellamy, Greg; McCrohon, Jane; Thomas, Paul; Bastian, B.; Chan, John; Lo, Gladys; Ho, Chi-Lai; Chan, Wai-Chi; Kwong, Raymond Y.; Parker, Anthony E.; Hauser, Thomas H.; Chan, Jimmy W.M.; Fong, Daniel Yee Tak; Lau, Chu‐Pak

doi:10.1093/eurheartj/ehm485

Cited by 176 publications

(168 citation statements)

References 32 publications

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“…38 This approach has been used in large animals studies 11,32,39 and in small clinical trials. [40][41][42][43] In line with the higher cell retention rates when delivered intramyocardially, a recent meta-analysis demonstrated that LVEF was improved by 8.4% when bone marrow progenitor cells were delivered directly to the myocardium. 44 In this study, we also validated a relevant preclinical model of myocardial hibernation.…”

Section: Discussionmentioning

confidence: 96%

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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M yocardial hibernation is a common clinical condition affecting patients with advanced coronary artery disease, 1 for whom cell-based therapies are targeted. In hibernation, repetitive episodes of ischemia and reperfusion lead to metabolic and functional changes in cardiomyocytes, ultimately impairing left ventricular (LV) function. Current therapies such as coronary artery bypass grafting or percutaneous coronary intervention are well established but not suitable for all patients; in previous clinical research from our group, more than one third of patients referred for revascularization did not undergo intervention because of unsuitable vessel anatomy, comorbidities, or other reasons.1 These patients are at high risk of cardiac events, and novel approaches such as cell-based vasculogenic therapy could provide them with an alternative form of therapy. Clinical Perspective on p 991Circulating angiogenic cells (CACs) constitute a heterogeneous population of peripheral blood-derived fibronectincultured cells. Although what defines their phenotype is still debated, 2 they were shown to uptake acetylated low-density lipoprotein, bind Ulex europaeus agglutinin-1 lectin, and express the pan-leukocyte marker CD45. They can also stain positive for monocyte/macrophage (CD14, CD11b/Mac-1, and CD11c) and endothelial (vascular endothelial growth factor receptor 2, von Willebrand factor, vascular endothelialcadherin, and CD31) markers. [3][4][5] Transplanted cells likely contribute to neovascularization through a paracrine mechanism by secreting and recruiting cardioprotective or proangiogenic growth factors. 6,7 The revascularization potential of Background-Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. Methods and Results-Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery.After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion resu...

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Section: Discussionmentioning

confidence: 96%

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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“…Angina frequency and exercise time were improved, but no clear effects on myocardial perfusion were observed. In the PROTECT-CAD trial (Tse et al, 2007), BMMC injections improved NYHA functional class, exercise time, LVEF, wall thickening and stress-induced perfusion defects. Finally, Van Ramshorst et al (van Ramshorst et al, 2009) reported better LVEF, myocardial perfusion, angina functional class, exercise capacity and quality of life after BMMC administration.…”

Section: Chronic Myocardial Ischemiamentioning

confidence: 96%

Randomized Clinical Trials in Stem Cell Therapy for the Heart - Old and New Types of Cells for Cardiovascular Repair

Sanz‐Ruiz¹,

Arranz²,

Ibañes³

et al. 2011

Stem Cells in Clinic and Research

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“…43,53,54,62 Heart Failure Additionally, there have been multiple HF trials (Table 2). Many demonstrated benefits in ventricular function noted by increased EF, [68][69][70][71][72][73]75,79,82,83 improved functional class, 75,78,80,82,83,86 reduced infarct size, 70,72,80,[82][83][84] decreased mortality, 79 and acceptable safety outcomes. [66][67][68][69]75,78,80,[82][83][84]86 SCIPIO was the first trial using autologous CSC in HF and showed improvement in EF, infarct size, viable tissue, and HF scores.…”

Section: Clinical Outcomes Acute Myocardial Infarctionmentioning

confidence: 99%

“…59,62 Intracoronary delivery has been used in AMI, 43 68,75 While others demonstrated no effect on EF, there were still benefits. 66,67,78,80,85,86 Using allogeneic multipotent cells via adventitial delivery, Penn et al 27 demonstrated a significant EF increase compared to results witnessed in other trials.…”

Section: Cell Delivery Comparisonsmentioning

confidence: 99%

Stem Cell Therapy for Heart Disease

2013

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Coronary artery disease is the leading cause of death in Americans. After myocardial infarction, significant ventricular damage persists despite timely reperfusion and pharmacological management. Treatment is limited, as current modalities do not cure this damage. In the past decade, stem cell therapy has emerged as a promising therapeutic solution to restore myocardial function. Clinical trials have demonstrated safety and beneficial effects in patients suffering from acute myocardial infarction, heart failure, and dilated cardiomyopathy. These benefits include improved ventricular function, increased ejection fraction, and decreased infarct size. Mechanisms of therapy are still not clearly understood. However, it is believed that paracrine factors, including stromal cell-derived factor-1, contribute significantly to stem cell benefits. The purpose of this article is to provide medical professionals with an overview on stem cell therapy for the heart and to discuss potential future directions.

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Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)

Abstract: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.

Cited by 176 publications

References 32 publications

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Randomized Clinical Trials in Stem Cell Therapy for the Heart - Old and New Types of Cells for Cardiovascular Repair

Stem Cell Therapy for Heart Disease

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