In situ electrostimulation drives a regenerative shift in the zone of infarcted myocardium.

Electrostimulation represents a well-known trophic factor for different tissues. In vitro electrostimulation of non-stem and stem cells induces myogenic predifferentiation and may be a powerful tool to generate cells with the capacity to respond to local areas of injury. We evaluated the effects of in vivo electrostimulation on infarcted myocardium using a miniaturized multiparameter implantable stimulator in rats.

Stem cells cardiac differentiation in 3D systems.

Cardiac regeneration requires a complex cascade of events. Stem cell therapy and tissue engineering are newly emerging tools with promising potential for recover or replace of damaged cardiac tissue. There are many factors, most of them still no clarified, that limit the effectiveness of these treatments and their translation to the clinic.

Potential clinical applications of adult human mesenchymal stem cell (Prochymal®) therapy.

In vitro, in vivo animal, and human clinical data show a broad field of application for mesenchymal stem cells (MSCs). There is overwhelming evidence of the usefulness of MSCs in regenerative medicine, tissue engineering, and immune therapy. At present, there are a significant number of clinical trials exploring the use of MSCs for the treatment of various diseases, including myocardial infarction and stroke, in which oxygen suppression causes widespread cell death, and others with clear involvement of the immune system, such as graft-versus-host disease, Crohn's disease, and diabetes.

A G-CSF functionalized PLLA scaffold for wound repair: An in vitro preliminary study.

Targeting wound repair, we developed an electrospun poly-L-lactide fibrous scaffold functionalized with G-CSF, a growth factor which is widely recognized as important in wound healing homeostasis. The scaffold was characterized in terms of morphology, mechanical properties and in vitro capacity to induce organization of co-cultures of murine fibroblasts and keratinocytes into a dermo-epidermal multilayered structure. Our findings are consistent with the promotion of a nonhostile environment, in which seeded cells could arrange themselves in an appropriate topographic distribution of elements at different levels of maturation up to a cornified epithelium on the top layer, resembling native skin.

A biomimetic three-layered compartmented scaffold for vascular tissue engineering.

Tissue engineering of vascular grafts still presents several shortcomings. Aiming to vascular regeneration, we developed a biomimetic multilayered scaffold with a middle pivotal collagen lamina between two functionalized layers of poly-L-lactide by means of electrospinning technique, with oriented drug-delivery capacity for the differentiation of human mesenchymal stem cells seeded therein. Applying appropriate cytokines, the inner layer is able to act as a drug delivery system in order to generate a pro-angiogenic and anti-thrombotic environment and the outer one is used to induce the media and adventitia generation.

Exploring new applications for Rhodiola rosea: can we improve the quality of life of patients with short-term hypothyroidism induced by hormone withdrawal?

Patients treated for differentiated thyroid cancer (DTC) are subjected to periodic surveillance that includes serum thyroglobulin measurements followed by radioiodine administrations for diagnostic and therapeutic purposes if necessary. Both procedures require adequately elevated blood levels of thyroid-stimulating hormone (TSH), which can be achieved by two approaches: parenteral administration of recombinant human TSH (rhTSH) or stopping thyroid hormone replacement until optimal levels of endogenous TSH are achieved. Although rhTSH administration does not require hormone withdrawal, it is not inexpensive and carries the risk of secondary effects.

Heparin-releasing scaffold for stem cells: a differentiating device for vascular aims.

Aims: Current limitations of tissue-engineered vascular grafts include timing for the scaffold preparation, cell type, cell differentiation and growth inside the construct, and thrombogenicity of the final device. To surmount these shortcomings, we developed a heparin-releasing poly-L-lactide (PLLA) scaffold using the electrospinning technique, to guide the differentiation of human mesenchymal stem cells towards the endothelial phenotype and to deliver a useful drug in the management of the postimplantation period.

Materials & Methods: The heparin-releasing PLLA scaffold was produced by means of the electrospinning technique in a tubular shape.

A G-CSF functionalized scaffold for stem cells seeding: a differentiating device for cardiac purposes.

Myocardial infarction and its consequences represent one of the most demanding challenges in cell therapy and regenerative medicine. Transfer of skeletal myoblasts into decompensated hearts has been performed through intramyocardial injection. However, the achievements of both cardiomyocyte differentiation and precise integration of the injected cells into the myocardial wall, in order to augment synchronized contractility and avoid potentially life-threatening alterations in the electrical conduction of the heart, still remain a major target to be pursued.

Comparative study of different techniques for the sterilization of poly-L-lactide electrospun microfibers: effectiveness vs. material degradation.

Electrospinning of biopolymeric scaffolds is a new and effective approach for creating replacement tissues to repair defects and/or damaged tissues with direct clinical application. However, many hurdles and technical concerns regarding biological issues, such as cell retention and the ability to grow, still need to be overcome to gain full access to the clinical arena. Interaction with the host human tissues, immunogenicity, pathogen transmission as well as production costs, technical expertise, and good manufacturing and laboratory practice requirements call for careful consideration when aiming at the production of a material that is available off-the-shelf, to be used immediately in operative settings.

Predifferentiated adult stem cells and matrices for cardiac cell therapy.

Stem cell therapy is a major field of research worldwide, with increasing clinical application, especially in cardiovascular pathology. However, the best stem cell source and type with optimal safety for functional engraftment remains unclear. An intermediate cardiac precommitted phenotype expressing some of the key proteins of a mature cardiomyocyte would permit better integration into the cardiac environment.

Atorvastatin increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study.

Endothelial progenitor cells (EPCs) are a subtype of hematopoietic stem cells, which contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC count in patients with coronary artery disease. Therefore, we investigated whether atorvastatin augments the number of EPCs after cardiopulmonary bypass (CPB) surgery.

Electrostimulated bone marrow human mesenchymal stem cells produce follistatin.

Background Aims: Follistatin (FST) and the related proteins FSTL1 and FSTL3 are crucial modulators of the transforming growth factor (TGF)-beta superfamily and function by neutralizing activins, a group of proteins implicated in many biologic processes, such as cell proliferation and differentiation, immune responses, various endocrine activities, wound repair, inflammation and fibrosis. Activins are increased in the serum of heart failure patients and in cardiomyocytes after experimental myocardial infarction, suggesting the involvement of activins in heart failure pathogenesis. FST is considered to be a key modulator in muscle development, differentiation and regeneration, and it has been implicated in the repair of mesodermal- and endodermal-derived tissues, promoting cell proliferation and hampering fibrogenesis.

Poly-L-lactic acid/hydroxyapatite electrospun nanocomposites induce chondrogenic differentiation of human MSC.

Cartilage and bone tissue engineering has been widely investigated but is still hampered by cell differentiation and transplant integration issues within the constructs. Scaffolds represent the pivotal structure of the engineered tissue and establish an environment for neo-extracellular matrix synthesis. They can be associated to signals to modulate cell activity.

Drug releasing systems in cardiovascular tissue engineering.

Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues.

Cardiac pre-differentiation of human mesenchymal stem cells by electrostimulation.

Myocardial repair using stem-cell therapy has become a promising therapeutic tool. However, many questions concerning a precise functional integration of injected cells remain unanswered. The use of cardiac pre-committed cells may improve integration, as these cells may complete their differentiation in the myocardium reducing fibrosis and restoring muscle function.

Electrostimulation induces cardiomyocyte predifferentiation of fibroblasts.

Stem-cell therapy has become a promising therapeutic tool for myocardial repair. Cardiac pre-committed cells, which complete their differentiation in the myocardium, may reduce fibrosis and restore muscle function. However, many questions concerning a precise, functional integration of injected cells remain unanswered.

Cell based approaches for myocardial regeneration and artificial myocardium.

Ischemic myocardial disease, the main cause of heart failure, is a major public health and economic problem. Given the aging population, heart failure is becoming an increasing clinical issue and a substantial financial burden. Thus, research in heart failure is of relevant interest and importance, involving specialties such as cellular and molecular biology, tissue engineering, genetics, biophysics and electrophysiology.

Stem cell therapy for the treatment of heart failure.

Purpose Of Review: Congestive heart failure is a complex clinical syndrome resulting from myocardial dysfunction that impairs the cardiovascular system's function. Medical and surgical therapy both still result in a large number of patients with very few options and persistent ventricular dysfunction. The major process to reverse ventricular remodeling would be the enhancement of regeneration of cardiac myocytes, as well as the stimulation of neovascularization within the affected area of the myocardium.

Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration.

The objective of cellular cardiomyoplasty is to regenerate the myocardium using implantation of living cells. Because the extracellular myocardial matrix is deeply altered in ischemic cardiomyopathies, it could be important to create a procedure aiming at regenerating both myocardial cells and the extracellular matrix. We evaluated the potential of a collagen matrix seeded with cells and grafted onto infarcted ventricles.

Autologous human serum for cell culture avoids the implantation of cardioverter-defibrillators in cellular cardiomyoplasty.

Background: Current clinical experience with cellular cardiomyoplasty (using serum bovine-cultivated myoblasts) has demonstrated significant malignant ventricular arrhythmias and sudden deaths in patients. In some ongoing clinical trials the implantation of cardioverter-defibrillator is mandatory. We have hypothesized that contact of human cells with fetal bovine serum results after 3-week fixation of animal proteins on the cell surface, representing an antigenic substrate for immunological and inflammatory adverse events.