Retrograde Coronary Venous Infusion as a Delivery Strategy in Regenerative Cardiac Therapy: an Overview of Preclinical and Clinical Data.
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SUBMITTER: Gathier WA
PROVIDER: S-EPMC5973989 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimBasic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model.Methods and resultsUnder hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).ConclusionsRetrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.
| S-EPMC4493537 | biostudies-literature
Project description:To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.
| S-EPMC4181717 | biostudies-literature
Project description:To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy.Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease.After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P = 0.008) and showed more pronounced effect estimates (P = 0.002). Higher citations were associated with journal impact factor (P = 0.007), corresponding author from North America/Europe (P = 0.022), and inclusion of nonrandomized trials (P = 0.046).Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.
| S-EPMC4484838 | biostudies-literature
Project description:The state-of-the-art approach to regenerating different tissues and organs is tissue engineering which includes the three parts of stem cells (SCs), scaffolds, and growth factors. Cellular behaviors such as propagation, differentiation, and assembling the extracellular matrix (ECM) are influenced by the cell's microenvironment. Imitating the cell's natural environment, such as scaffolds, is vital to create appropriate tissue. Craniofacial tissue engineering refers to regenerating tissues found in the brain and the face parts such as bone, muscle, and artery. More biocompatible and biodegradable scaffolds are more commensurate with tissue remodeling and more appropriate for cell culture, signaling, and adhesion. Synthetic materials play significant roles and have become more prevalent in medical applications. They have also been used in different forms for producing a microenvironment as ECM for cells. Synthetic scaffolds may be comprised of polymers, bioceramics, or hybrids of natural/synthetic materials. Synthetic scaffolds have produced ECM-like materials that can properly mimic and regulate the tissue microenvironment's physical, mechanical, chemical, and biological properties, manage adherence of biomolecules and adjust the material's degradability. The present review article is focused on synthetic materials used in craniofacial tissue engineering in recent decades.
| S-EPMC9681815 | biostudies-literature
Project description:BackgroundThe purpose of this study was to illustrate the additive value of computed tomography angiography (CTA) for visualisation of the coronary venous anatomy prior to cardiac resynchronisation therapy (CRT) implantation.MethodsEighteen patients planned for CRT implantation were prospectively included. A specific CTA protocol designed for visualisation of the coronary veins was carried out on a third-generation dual-source CT platform. Coronary veins were semi-automatically segmented to construct a 3D model. CTA-derived coronary venous anatomy was compared with intra-procedural fluoroscopic angiography (FA) in right and left anterior oblique views.ResultsCoronary venous CTA was successfully performed in all 18 patients. CRT implantation and FA were performed in 15 patients. A total of 62 veins were visualised; the number of veins per patient was 3.8 (range: 2-5). Eighty-five per cent (53/62) of the veins were visualised on both CTA and FA, while 10% (6/62) were visualised on CTA only, and 5% (3/62) on FA only. Twenty-two veins were present on the lateral or inferolateral wall; of these, 95% (21/22) were visualised by CTA. A left-sided implantation was performed in 13 patients, while a right-sided implantation was performed in the remaining 2 patients because of a persistent left-sided superior vena cava with no left innominate vein on CTA.ConclusionImaging of the coronary veins by CTA using a designated protocol is technically feasible and facilitates the CRT implantation approach, potentially improving the outcome.
| S-EPMC6115304 | biostudies-literature
Project description:Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.
| S-EPMC5329741 | biostudies-literature
Project description:Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction. Currently, it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration. To understand how interstitial cells behave during this process, we performed single-cell RNA sequencing of regenerating zebrafish hearts. Using a combination of immunohistochemistry, chemical inhibition, and novel transgenic animals, we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration. This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations. Here, we provide detailed insight into how interstitial cells behave during cardiac regeneration, which will serve to increase our understanding of how this process could eventually be induced in humans.
| S-EPMC10068904 | biostudies-literature
Project description:The photon-counting detector (PCD) is a new computed tomography detector technology (photon-counting computed tomography, PCCT) that provides substantial benefits for cardiac and coronary artery imaging. Compared with conventional CT, PCCT has multi-energy capability, increased spatial resolution and soft tissue contrast with near-null electronic noise, reduced radiation exposure, and optimization of the use of contrast agents. This new technology promises to overcome several limitations of traditional cardiac and coronary CT angiography (CCT/CCTA) including reduction in blooming artifacts in heavy calcified coronary plaques or beam-hardening artifacts in patients with coronary stents, and a more precise assessment of the degree of stenosis and plaque characteristic thanks to its better spatial resolution. Another potential application of PCCT is the use of a double-contrast agent to characterize myocardial tissue. In this current overview of the existing PCCT literature, we describe the strengths, limitations, recent applications, and promising developments of employing PCCT technology in CCT.
| S-EPMC10253312 | biostudies-literature
Project description:BackgroundCerebral venous sinus thrombosis (CVST) is a rare and often misdiagnosed condition with mortality rates ranging from 6 to 10%. Diagnosis and monitoring are typically achieved through noninvasive imaging, including computed tomography or magnetic resonance venography. The current standard of treatment is systemic anticoagulation. However, in patients who continue to decline neurologically or do not show sufficient response to or have absolute contraindications to systemic anticoagulation, endovascular treatments are an alternative. Endovascular options are poorly studied and specific devices have not been developed, partially due to the rare nature of the disease. Here, we present a case report detailing the treatment of extensive CVST from the vein of Galen to the sigmoid sinus using mechanical thrombectomy and local infusions of unfractionated heparin (UFH) and tissue plasminogen activator.Case descriptionA 53-year-old man presented and was found to have extensive CVST extending from the vein of Galen to the left sigmoid sinus. Systemic UFH was begun; however, his condition continued to decline, and he was taken for endovascular intervention, wherein mechanical thrombectomy was undertaken using combinations of stent retrievers and balloon catheters, which provided acceptable revascularization. Unfortunately, his hospital course was further complicated by a cerebellar hematoma that was surgically evacuated and reocclusion of the sinus for which a microcatheter was placed for infusion of UFH and tissue plasminogen activator.ConclusionComplicated CVST may require aggressive endovascular management. Local infusions of heparin and thrombolytic agents as well as mechanical thrombectomy are safe alternative options.
| S-EPMC7395561 | biostudies-literature
Project description:We present a case with coronary bypass grafts in which venous graft was anastomosed to obtuse marginal (OM) 1 and OM2 branches sequentially. We performed percutaneous intervention to the proximal circumflex (CX), OM1, and bridging segment of the venous graft. Finally, bridging segment of the venous graft began to function as a CX body extending between the OM1 and OM2.
| S-EPMC4244237 | biostudies-other