Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133
            <sup>+</sup>
            Progenitors Expanded From the Peripheral Blood

Suuronen, Erik J.; Veinot, John P.; Wong, Serena; Kapila, Varun; Price, Joel; Griffith, May; Mesana, Thierry G.; Ruel, Marc

doi:10.1161/circulationaha.105.001081

Cited by 126 publications

(99 citation statements)

References 24 publications

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“…In this regard, we have previously demonstrated by tracking cells with PET and by histology that our collagen-based matrix can improve cell retention and prevent excessive relocation of transplanted cells to nontarget tissues, 36 in addition to improving capillary density. 14 We also previously showed that CACs exposed to the matrix demonstrated higher levels of phosphorylated Akt (PI3K/Akt pathway) and increased survival under hypoxia. 15 Based on the ability of the collagen matrix to modulate the therapeutic phenotype and function of CACs, it may have induced similar effects in the pig model of this study.…”

Section: Discussionmentioning

confidence: 86%

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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: 86%

“…14 In the present study, we induced and validated a preclinical model of myocardial ischemia and hibernation and used it to investigate the benefits of biopolymer-supported CAC delivery in this clinically relevant setting.…”

mentioning

confidence: 99%

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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“…Moreover, it is likely that a new appreciation for the mechanisms of action of current conventional pharmacological agents such as ACE inhibitors and statins will emerge with respect to matrix remodeling. In addition, it is becoming recognized that the structure and function of the interstitium play a critical role in the viability and phenotype of transplanted cells into the myocardium (212,430). Thus it is likely that improved understanding of myocardial matrix remodeling and degradation pathways will facilitate the development of pharmacological as well as cell-based treatment strategies for LV remodeling.…”

Section: The Myocardial Matrix As a Dynamic Entity Influencing Carmentioning

confidence: 99%

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

998

1,023

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It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

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“…Microvascular wall thickness and lumen diameter were measured and their ratio calculated (18). In addition, capillary density was assessed in hematoxylin and eosin-stained sections under ϫ1,000 magnification as the ratio of capillaries to muscle fibers, as previously described (35,40).…”

Section: Methodsmentioning

confidence: 99%

Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction

Caceres

Lin

Zhu

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Coronary artery disease is a leading cause of death. Hypertension (HT) increases the incidence of cardiac events, but its effect on cardiac adaptation to coexisting coronary artery stenosis (CAS) is unclear. We hypothesized that concurrent HT modulates microvascular function in chronic CAS and aggravates microvascular remodeling and myocardial injury. Four groups of pigs ( n = 6 each) were studied: normal, CAS, HT, and CAS+HT. CAS and HT were induced by placing local irritant coils in the left circumflex coronary artery and renal artery, respectively. Six weeks later multidetector computerized tomography (CT) was used to assess systolic and diastolic function, microvascular permeability, myocardial perfusion, and responses to adenosine in the “area at risk.” Microvascular architecture, inflammation, and fibrosis were then explored in cardiac tissue. Basal myocardial perfusion was similarly decreased in CAS and CAS+HT, but its response to adenosine was significantly more attenuated in CAS. Microvascular permeability in CAS+HT was greater than in CAS and was accompanied by amplified myocardial inflammation, fibrosis, and microvascular remodeling, as well as cardiac systolic and diastolic dysfunction. On the other hand, compared with normal, micro-CT-derived microvascular (20–200 μm) transmural density decreased in CAS but not in HT or CAS+HT. We conclude that the coexistence of early renovascular HT exacerbated myocardial fibrosis and vascular remodeling distal to CAS. These changes were not mediated by loss of myocardial microvessels, which were relatively preserved, but possibly by exacerbated myocardial inflammation and fibrosis. HT modulates cardiac adaptive responses to CAS and bears cardiac functional consequences.

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Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133 ⁺ Progenitors Expanded From the Peripheral Blood

Cited by 126 publications

References 24 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

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction

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Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133 + Progenitors Expanded From the Peripheral Blood

Cited by 126 publications

References 24 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

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction

Contact Info

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Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133 ⁺ Progenitors Expanded From the Peripheral Blood