Current Stem Cell Research & Therapy - Volume 12, Issue 2, 2017

Cardiovascular diseases (CVD) are the main object of morbidity and death in the world. There are different triggers of CVD, but atherosclerosis and/or hypertension are the most usual. CVD risk factors are used as prognosticators of disease process, while the biomarkers that envisage cardiovascular risk have an important biological basis. The integration of CVD risk factors and new biomarkers can improve CVD risk stratification and disease management. The identification of microparticles (MPs) in body fluids has opened new perspectives in diagnosis, prognosis and therapy of CVD pathogenesis. MPs are submicron vesicles released from a diversity of cell types with pleiotropic biological effects on signaling among cells. They are correlated with disease state and play a major role in atherosclerosis associated with inflammation, thrombosis as well as in CVD development and progression. This review reveals many sides of MPs as risk factors, biomarkers, novel forms of intercellular communication, non-invasive potential diagnostic tools and discusses their positive and negative impact on CVD.

Template-mediated mineralization describes a research field of materials chemistry that deals with templates influencing product formation of foremost inorganic functional materials and composites. These templates are usually organic compounds - as far as molecules with natural origin are involved, the terminology "biomineralization" or "biomimetic mineralization" is used. The present review gives insight into recent developments in the research area of bone-tissue engineering with focus on chemical templates and cell-based approaches. The review is structured as follows: (1) a brief general overview about the principle of templating and recently used template materials, (2) important analytical methods, (3) examples of template-guided mineralization of various bone-related materials, (4) natural bone mineralization, (5) scaffolds for bone-tissue regeneration and (6) cell-based therapeutic approaches. For this purpose, a literature screening with emphasis on promising potential practical applications was performed. In particular, macromolecular structures and polymer composites with relation to naturally occurring compounds were favored. Priority was given to publications of the last five years. Although the present review does not cover the whole topic to full extent, it should provide information about current trends and the most promising approaches in the research area of bone-tissue engineering based on applications of organic templates/scaffolds as well as cell-based strategies.

Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

In modern society, myocardial infarction is a major cause of mortality, morbidity and deterioration of quality of life. Although various therapeutic approaches are available, none of them lead to the regeneration of infarcted tissue. The use of mesenchymal stem cells in cell therapy for myocardial infarction showed a beneficial effect consisting in reduced infarcted area and improved cardiac function, which can be explained by paracrine mechanism. It has been shown that stem cells are able to release a very complex range of factors including growth factors, cytokines and chemokines, along with an abundant mixture of membrane vesicles. These secreted elements contribute to the beneficial effect of stem cells therapy observed both in vitro and in vivo. Recent studies have shown that exosomes, which are small membrane vesicles originating in the endocytic pathway of the cells and carry a complex cargo consisting in mRNA, microRNA and various other anti-apoptotic and pro-angiogenic factors, are the main mediators of stem cells paracrine effect. In this review, we discuss the capacity of mesenchymal stem cells to protect the ischemic myocardium, the role of exosomes as protective factors secreted by stem cells and the possibility to use these vesicles in developing a novel approach in cardiovascular therapy, involving a non-cellular use of mesenchymal stem cells paracrine activity.

Understanding the spatiotemporal dynamics of stem cell fate regulation is important for both fundamental biology and for directing the generation of a specific phenotype during the fabrication of tissue engineering materials. Recent findings revealed aspects of extracellular signals transduction by mesenchymal stem cells that are further integrated to modulate their lineage specification. This review focuses on recent developments in the field of nanobiomaterials design and fabrication for use in research and therapy of bone tissue. Also, new methods of assessment of stem cell multipotency or differentiated phenotype developed for clinical quality control applications are described. Materials engineered for understanding fundamental mechanisms of stem cell interaction with substrates are highlighted as key studies to drive advances in bone implants design. The use of polymers with defined biomechanical and topographical features to mimic the extracellular matrix biochemistry or biophysical cues is discussed. Bioengineered scaffolds able to induce osteogenic fate of bone marrow-derived mesenchymal stem cells in the absence of differentiation factors are successful models for potential development of implant biomaterials with enhanced osseointegration capacity and decreased soft tissue encapsulation.

The number of ligament injuries increases every year and concomitantly the need for materials or systems that can reconstruct the ligament. Limitations imposed by autografts and allografts in ligament reconstruction together with the advances in materials science and biology have attracted a lot of interest for developing systems and materials for ligament replacement or reconstruction. This review intends to synthesize the major steps taken in the development of polymer-based materials for anterior cruciate ligament, their advantages and drawbacks and the results of different in vitro and in vivo tests. Until present, there is no successful polymer system for ligament reconstruction implanted in humans. The developing field of synthetic polymers for ligament reconstruction still has a lot of potential. In addition, several nano-structured materials, made of nanofibers or in the form of ceramic/polymeric nanocomposites, are attracting the interest of several groups due to their potential use as engineered scaffolds that mimic the native environment of cells, increasing the chances for tissue regeneration. Here, we review the last 15 years of literature in order to obtain a better understanding on the state-of-the-art that includes the usage of nano- and poly-meric materials for ligament reconstruction, and to draw perspectives on the future development of the field.

Cardiovascular diseases remain the leading cause of mortality or disabled quality of life for people over the world. The necessity of neovascularization is essential for re-establishing the tissue functions after a major lesion that occurs in patients with cardiovascular disorders, such as ischemia, atherosclerosis, diabetes, peripheral vascular disease and burn wounds. This review focuses on the recent data regarding the polymers and scaffolds that are used for improving neovascularization with emphasis on the biocompatibility and mechanisms involved in stem cells proliferation, migration, adherence, differentiation and organization in vascular networks. The newly emerging techniques used in conjugation of synthetic polymers with polysaccharides or proteins attempt to improve the biocompatibility of scaffolds, but the complex structures of blood vessels make their construction to remain a major challenge for the vascular tissue engineering.

The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered.

The objective of this study was to investigate the effects of P. aeruginosa PAO1 cellular and soluble culture fractions on human mesenchymal stem cells (MSCs) death signaling pathways and cytokine profile. The bone marrow isolated MSCs, incubated for different periods of time with one of the three P. aeruginosa PAO1 culture fractions, i.e. low density whole cultures, heat inactivated bacterial cultures sediments and sterile supernatants, were submitted to the following assays: i) fluorescence microscopy evaluation of cellular morphology and viability; ii) bax, caspase 9, relA and bcl-2 genes expression analysis by qRT-PCR; and iii) quantification of the level of IL-1β, IL-6, IL-8 and IL-10 cytokines released in the MSCs supernatants determined by ELISA. Results were statistically analyzed using the GraphPad In Stat software. The PAO1 whole cultures exhibited the most relevant influences, impacting on MSCs morphology and viability, interfering with apoptotic pathways and significantly stimulating the production of IL-1β and IL-10, while decreasing the production of IL-6 and IL-8. The culture supernatants increased the production of IL-1β and reduced the secretion of all other tested cytokines, while heat-inactivated bacterial cells significantly stimulated both IL-1β and IL-10 production. These data could suggest that in vivo, the fate of P. aeruginosa infection depends on the proportion between different bacterial culture fractions (i.e. the number of viable bacterial cells, the number of dead cells and the amount of bacterial soluble products accumulated locally) that could be influenced by the initial infective dose, by the host defense mechanisms, and also by the administered antimicrobial treatment that may thus interfere with the evolution and magnitude of the induced lesions.