Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells (PICs) Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs) express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs) significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Stamceltherapie voor het beschadigde hart

Current therapies for ischemic heart failure are not sufficient. Regenerative therapy is a promising strategy that has rapidly developed into a clinical phase. Although the exact mechanism of action is not entirely understood, clinical results show a statistically significant effect of stem cells in ischemic heart diseases. At this moment there is no consensus on the clinical relevance of stem cell therapy. In this review we discuss the rationale for stem cell therapy. We will focus on autologous bone marrow cells in clinical setting. Finally, we will give an overview of new developments that will optimize future cell therapy

Diffusion Tensor MRI of the Heart – In Vivo Imaging of Myocardial Fiber Architecture

Despite many difficulties, the field of cardiac diffusion imaging is slowly but steadily making progress. In recent years it was demonstrated that reproducible measurement of diffusion parameters and fiber architecture in healthy and diseased hearts is possible. In this review we will discuss the basics of diffusion imaging as well as various reconstruction and analysis models. Furthermore, we cover the main challenges and proposed solutions that come with in vivo cardiac diffusion imaging. In vivo and ex vivo diffusion imaging of the heart has shown that the technique has great potential to better understand cardiac function, characterize cardiac pathology, and understand myofiber remodeling in response to injury or disease

3D Hybrid Imaging for Structural and Congenital Heart Interventions in the Cath Lab

Hybrid imaging (HI) during cardiovascular interventions enables the peri-procedural visualization of the organs and tissues by means of integrating different imaging modalities. HI can improve the procedural efficacy and safety. This review provides an overview of different systems, their possibilities and the current clinical use and benefits focused on structural and congenital heart diseases. We have performed a literature search and linked the software options to the clinical use in cardiology to gain insight into the clinical use of the systems. In this review, we focus on radiation and contrast exposure, complication rate and procedure time. We found that currently available studies are limited by small cohorts. Nevertheless, HI systems for valvular procedures result in a significant decrease of radiation and contrast exposure. The largest benefit hereof is observed when HI is used in combination with rotational angiography. Furthermore, automatically determined optimal implant angle for transcatheter aortic valve implantation decreases the complication rate significantly. Congenital heart disease interventions that require 2D/3D Transoesophageal echocardiography (TEE) such as septal defects show a significant decrease in radiation and contrast exposure and procedural time when using TEE-Mono- and bi-plane cine angiography and fluoroscopy (XRF) fusion software. MitraClip procedures using these HI systems, however, show only a trend in decrease of these effects. In conclusion, major interventional X-ray vendors offer HI software solutions which are safe and can aid the planning and image guidance of cardiovascular interventions. Even though current HI technologies have limitations, HI provides support in the increasingly complex cardiac interventional procedures to provide better patient care

3D Hybrid Imaging for Structural and Congenital Heart Interventions in the Cath Lab

Hybrid imaging (HI) during cardiovascular interventions enables the peri-procedural visualization of the organs and tissues by means of integrating different imaging modalities. HI can improve the procedural efficacy and safety. This review provides an overview of different systems, their possibilities and the current clinical use and benefits focused on structural and congenital heart diseases. We have performed a literature search and linked the software options to the clinical use in cardiology to gain insight into the clinical use of the systems. In this review, we focus on radiation and contrast exposure, complication rate and procedure time. We found that currently available studies are limited by small cohorts. Nevertheless, HI systems for valvular procedures result in a significant decrease of radiation and contrast exposure. The largest benefit hereof is observed when HI is used in combination with rotational angiography. Furthermore, automatically determined optimal implant angle for transcatheter aortic valve implantation decreases the complication rate significantly. Congenital heart disease interventions that require 2D/3D Transoesophageal echocardiography (TEE) such as septal defects show a significant decrease in radiation and contrast exposure and procedural time when using TEE-Mono- and bi-plane cine angiography and fluoroscopy (XRF) fusion software. MitraClip procedures using these HI systems, however, show only a trend in decrease of these effects. In conclusion, major interventional X-ray vendors offer HI software solutions which are safe and can aid the planning and image guidance of cardiovascular interventions. Even though current HI technologies have limitations, HI provides support in the increasingly complex cardiac interventional procedures to provide better patient care