Knowledge Of Cell Biology Research Articles

Therapeutic efficacy of mesenchymal stem cells for cardiovascular diseases

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy of CVDs. In particular, we analyze the biological properties of MSCs, elucidate recent clinical findings and clinical trial phases of investigation, highlight clinical therapeutic effects of MSCs, and discuss challenges towards the clinical use of these cells in the therapy of CVDs.

New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology.

NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challenges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technological advancements in gene delivery, gene editing and chimeric antigen receptors (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable “off-the-shelf” products with fewer side effects. In this review, we highlight recent advances in NK cell biology along with current approaches for potentiating NK cell proliferation and activity, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy.

Diagnosis and treatment of cystic fibrosis in pulmonology

Agnė Pacevičiūtė1, Skaidra Bieliūnaitė1, Dalia Balčienė2 1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine 2Vilnius University Hospital Santaros Clinics, Centre of Pulmonology and Allergology Abstract Introduction. Cystic fibrosis is one of the most common of life-shortening genetic diseases, inherited in an autosomal recessive manner and caused by mutations that lead to the accumulation of sticky mucus in the respiratory system. Progressive respiratory failure remains the primary source of mortality, therefore it is important to understand the effects of this disease on the respiratory system. Aim: to review the cystic fibrosis diagnosis and treatment. Methodology: the literature used for this review was selected using the “Pubmed” database. The literature search was conducted using selected keywords, the most relevant and recent articles were selected. More than 30 publications on cystic fibrosis were analyzed. Results. Cystic fibrosis is a life-threatening disease that requires clinical symptoms, family history, laboratory and instrumental tests to confirm the diagnosis. Treatment for cystic fibrosis is evolving rapidly from symptomatic treatment to drugs that modulate the CFTR protein. Conclusions: Cystic fibrosis is one of the most common of life-shortening genetic diseases, inherited in an autosomal recessive manner and caused by a CFTR mutation. Disease manifests in reccurent wheezing, dyspnea, pneumonia, bronchiolitis and bronchiectasis. The sweat test is the primary laboratory test. Antibiotics, anti-inflammatories, mucolytics only treat the manifestations of the disease, but fundamental knowledge of molecular and cell biology has increased the prospects of targeted therapy. Keywords: cystic fibrosis, cystic fibrosis gene, newborn screening, sweat test, Ivacaftor.

Drosophila, an Integrative Model to Study the Features of Muscle Stem Cells in Development and Regeneration

Muscle stem cells (MuSCs) are essential for muscle growth, maintenance and repair. Over the past decade, experiments in Drosophila have been instrumental in understanding the molecular and cellular mechanisms regulating MuSCs (also known as adult muscle precursors, AMPs) during development. A large number of genetic tools available in fruit flies provides an ideal framework to address new questions which could not be addressed with other model organisms. This review reports the main findings revealed by the study of Drosophila AMPs, with a specific focus on how AMPs are specified and properly positioned, how they acquire their identity and which are the environmental cues controlling their behavior and fate. The review also describes the recent identification of the Drosophila adult MuSCs that have similar characteristics to vertebrates MuSCs. Integration of the different levels of MuSCs analysis in flies is likely to provide new fundamental knowledge in muscle stem cell biology largely applicable to other systems.

Rethinking lysosomes and lysosomal disease

Lysosomal storage diseases were recognized and defined over a century ago as a class of disorders affecting mostly children and causing systemic disease often accompanied by major neurological consequences. Since their discovery, research focused on understanding their causes has been an important driver of our ever-expanding knowledge of cell biology and the central role that lysosomes play in cell function. Today we recognize over 50 so-called storage diseases, with most understood at the level of gene, protein and pathway involvement, but few fully clarified in terms of how the defective lysosomal function causes brain disease; even fewer have therapies that can effectively rescue brain function. Importantly, we also recognize that storage diseases are not simply a class of lysosomal disorders all by themselves, as increasingly a critical role for the greater lysosomal system with its endosomal, autophagosomal and salvage streams has also emerged in a host of neurodevelopmental and neurodegenerative diseases. Despite persistent challenges across all aspects of these complex disorders, and as reflected in this and other articles focused on lysosomal storage diseases in this special issue of Neuroscience Letters, the progress and promise to both understand and effectively treat these conditions has never been greater.

Tissue regulatory T cells: regulatory chameleons.

The FOXP3+CD4+ regulatory T (Treg) cells located in non-lymphoid tissues differ in phenotype and function from their lymphoid organ counterparts. Tissue Treg cells have distinct transcriptomes, T cell receptor repertoires and growth and survival factor dependencies that arm them to survive and operate in their home tissue. Their functions extend beyond immune surveillance to tissue homeostasis, including regulation of local and systemic metabolism, promotion of tissue repair and regeneration, and control of the proliferation, differentiation and fate of non-lymphoid cell progenitors. Treg cells in diverse tissues share a common FOXP3+CD4+ precursor located within lymphoid organs. This precursor undergoes definitive specialization once in the home tissue, following a multilayered array of common and tissue-distinct transcriptional programmes. Our deepening knowledge of tissue Treg cell biology will inform ongoing attempts to harness Treg cells for precision immunotherapeutics.

Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

Animal models have contributed greatly to our understanding of human diseases. Here, we focus on cornea epithelial stem cell (CESC) deficiency (commonly called limbal stem cell deficiency, LSCD). Corneal development, homeostasis and wound healing are supported by specific stem cells, that include the CESCs. Damage to or loss of these cells results in blindness and other debilitating ocular conditions. Here we describe the contributions from several vertebrate models toward understanding CESCs and LSCD treatments. These include both mammalian models, as well as two aquatic models, Zebrafish and the amphibian, Xenopus. Pioneering developments have been made using stem cell transplants to restore normal vision in patients with LSCD, but questions still remain about the basic biology of CESCs, including their precise cell lineages and behavior in the cornea. We describe various cell lineage tracing studies to follow their patterns of division, and the fates of their progeny during development, homeostasis, and wound healing. In addition, we present some preliminary results using the Xenopus model system. Ultimately, a more thorough understanding of these cornea cells will advance our knowledge of stem cell biology and lead to better cornea disease therapeutics.

NanoBioscaffolds as Wound Healing Biomaterials in Animals

Background: Tissue-engineered scaffolds for skin wound healing have undergone marvelous progress. The recognition that a three-dimensional scaffold more closely mimics the biomechanical environment of wounds and advancing knowledge of cell biology has led to the next-generation of engineered bioscaffolds with nanotechnology. A unifying approach is required for the translational success of bioscaffolds, involving clinicians, biologists and chemists. The decellularized materials were expanding their clinical utility due to high clinical results ahead of the ones with autografts. They are gradually gaining market space due to their ease of standardized production, constant availability for grafting and biomechanical/ biochemical advantage. Hence, the present study aimed to develop biobased decellularized extracellular matrix (dECM) impregnated with eco-friendly synthesized silver nanoparticles and then to evaluate their wound healing activity the excision wound model of rats. Methods: The dECM was prepared to achieve acellularity, intactness and adequate tensile strength. The same was confirmed by morphological (histology, scanning electron microscopy and Fourier transform infrared spectroscopy), mechanical (tensile strength) and biological (DNA quantification) analyses. Further, the dECM was impregnated with the eco-friendly synthesized keratin-chitosan-silver nanoparticles to produce ‘NanoBioscaffolds’ for extended biocompatibility and were evaluated for wound healing activity in rats. Result: The findings of the histopathology (H and E staining), immunohistochemistry (the proliferative activity of keratinocytes by Ki67 staining) and biochemical analysis (anti oxidative status by catalase estimation) revealed that wound healing activity was promoted by inducing proliferation and migration of the keratinocytes and detoxification of reactive oxygen species activity (ROS) in NanoBioscaffold treated group.

高中细胞知识与细胞生物学知识的衔接比较

高中细胞知识与细胞生物学知识的衔接比较

A 3D printed in vitro bone model for the assessment of molecular and cellular cues in metastatic neuroblastoma.

Metastasis is a complex and multifactorial process highly dependent on the interaction between disseminated tumor cells and the pre-metastatic niche. The metastatic sites detected in the bone of patients affected by neuroblastoma (NB), a malignancy of the developing sympathetic nervous system, are particularly aggressive. To improve our current knowledge of metastatic tumor cell biology and improve treatment success, appropriate in vitro and in vivo models that more closely resemble the native metastatic niche are needed. In this study, the impact of the geometry of synthetic β-tricalcium-phosphate (β-TCP) structures on the interaction of NB tumor cells with the stromal component has been examined. The tumor microenvironment is dynamically shaped by the stroma, which sustains the growth of NB cells inside the metastatic niche. The 3D growth conditions are a determining factor for the cell proliferation rate in β-TCP. With respect to planar counterparts, channeled 3D β-TCP structures stimulate more interleukin-6 and Fibronectin production and define Connexin 43 distribution inside the cells. Together, these results highlight how the biomechanical properties of the 3D microenvironment enable tumor cells to form spheroid-shaped arrangements. This, in turn, facilitates their pro-migratory and pro-invasive patterns and mimics the in vivo situation by translating realistic mechanobiological cues to the metastatic NB.

Effect of Age and Lipoperoxidation in Rat and Human Adipose Tissue-Derived Stem Cells.

A wide range of clinical applications in regenerative medicine were opened decades ago with the discovery of adult stem cells. Highly promising adult stem cells are mesenchymal stem/stromal cells derived from adipose tissue (ADSCs), primarily because of their abundance and accessibility. These cells have multipotent properties and have been used extensively to carry out autologous transplants. However, the biology of these cells is not entirely understood. Among other factors, the regeneration capacity of these cells will depend on both their capacity of proliferation/differentiation and the robustness of the biochemical pathways that allow them to survive under adverse conditions like those found in damaged tissues. The transcription factors, such as Nanog and Sox2, have been described as playing an important role in stem cell proliferation and differentiation. Also, the so-called longevity pathways, in which AMPK and SIRT1 proteins play a crucial role, are essential for cell homeostasis under stressful situations. These pathways act by inhibiting the translation through downregulation of elongation factor-2 (eEF2). In order to deepen knowledge of mesenchymal stem cell biology and which factors are determinant in the final therapeutic output, we evaluate in the present study the levels of all of these proteins in the ADSCs from humans and rats and how these levels are affected by aging and the oxidative environment. Due to the effect of aging and oxidative stress, our results suggest that before performing a cell therapy with ADSCs, several aspects reported in this study such as oxidative stress status and proliferation and differentiation capacity should be assessed on these cells. This would allow us to know the robustness of the transplanted cells and to predict the therapeutic result, especially in elder patients, where probably ADSCs do not carry out their biological functions in an optimal way.

Emerging applications at the interface of DNA nanotechnology and cellular membranes: Perspectives from biology, engineering, and physics.

DNA nanotechnology has proven exceptionally apt at probing and manipulating biological environments as it can create nanostructures of almost arbitrary shape that permit countless types of modifications, all while being inherently biocompatible. Emergent areas of particular interest are applications involving cellular membranes, but to fully explore the range of possibilities requires interdisciplinary knowledge of DNA nanotechnology, cell and membrane biology, and biophysics. In this review, we aim for a concise introduction to the intersection of these three fields. After briefly revisiting DNA nanotechnology, as well as the biological and mechanical properties of lipid bilayers and cellular membranes, we summarize strategies to mediate interactions between membranes and DNA nanostructures, with a focus on programmed delivery onto, into, and through lipid membranes. We also highlight emerging applications, including membrane sculpting, multicell self-assembly, spatial arrangement and organization of ligands and proteins, biomechanical sensing, synthetic DNA nanopores, biological imaging, and biomelecular sensing. Many critical but exciting challenges lie ahead, and we outline what strikes us as promising directions when translating DNA nanostructures for future in vitro and in vivo membrane applications.

A light way for nuclear cell biologists.

The nucleus is a very complex organelle present in eukaryotic cells. Having the crucial task to safeguard, organize and manage the genetic information, it must tightly control its molecular constituents, its shape and its internal architecture at any given time. Despite our vast knowledge of nuclear cell biology, much is yet to be unravelled. For instance, only recently we came to appreciate the existence of a dynamic nuclear cytoskeleton made of actin filaments that regulates processes such as gene expression, DNA repair and nuclear expansion. This suggests further exciting discoveries ahead of us. Modern cell biologists embrace a new methodology relying on precise perturbations of cellular processes that require a reversible, highly spatially confinable, rapid, inexpensive and tunEable external stimulus: light. In this review, we discuss how optogenetics, the state-of-the-art technology that uses genetically encoded light-sensitive proteins to steer biological processes, can be adopted to specifically investigate nuclear cell biology.

Staining and Tracking Methods for Studying Sponge Cell Dynamics.

To better understand the origin of animal cell types, body plans, and other morphological features, further biological knowledge and understanding are needed from non-bilaterian phyla, namely, Placozoa, Ctenophora, and Porifera. This chapter describes recent cell staining approaches that have been developed in three phylogenetically distinct sponge species-the homoscleromorph Oscarella lobularis, and the demosponges Amphimedon queenslandica and Lycopodina hypogea-to enable analyses of cell death, proliferation, and migration. These methods allow for a more detailed understanding of cellular behaviors and fates, and morphogenetic processes in poriferans, building on current knowledge of sponge cell biology that relies chiefly on classical (static) histological observations.

Review on Potential of Reproductive Technology to Improved Ruminant Production in Ethiopia

DOI: 10.7176/JBAH/10-8-02 Publication date: April 30 th 2020 INTRODUCTION Reproductive technology encompasses all current and anticipated uses of technology in human and animal reproduction, including assisted reproductive technology, contraception and others (Mapletoft and Hasler, 2005). Research into physiology and embryology has provided a basis for the development of technologies that increase productivity of farm animals through enhanced control of reproductive function. Animal Biotechnology represents an expanding collection of rapidly developing disciplines in science and information technologies. The livestock provides many opportunities to utilize these disciplines and evolving competencies. Individually, these are powerful tools capable of providing significant improvements in productivity. Combinations of these technologies coupled with information systems and data analysis will provide even more significant changes in the next decade. Various techniques have been developed and refined to obtain a large number of offspring from genetically superior animals or obtain offspring from infertile (or sub fertile) animals (Naqvi et al ., 2001; Blackburn, 2004). Based on the progress in scientific knowledge of endocrinology, reproductive physiology, cell biology and embryology during the last fifty years new bio techniques have been developed for and introduced into animal breeding and husbandry (Wrathall et al ., 2004). Among them are estrus synchronization/induction, artificial insemination, Multiple Ovulation Induction and Embryo Transfer (MOET), in vitro embryo production (IVP) and cloning by Nuclear Transfer (NT) all are components of the tool box for present and future applications (Betteridge, 2003). Techniques are now available to get genetically improved farm animals in large numbers. This involves collection of the fertilized egg from genetically superior female which ovulate spontaneously or are induced to super ovulate (Wolf et al . , 2000). The current efficiency for producing transgenic animals particularly farm animals, is low and the cost is high. Success in the production of transgenic farm animals requires an adequate animal facility and dedicated teams of embryologists, veterinarians, animal scientists and molecular biologists. Ethiopia has over 57.83 million indigenous cattle, and about 13.5million are breeder cows and 28.89 million sheep out of which about 14 Million are kept for breeder and 29.7 million goats out of this 12.6 million are kept for breeder (CSA, 2015/16). Average milk production from local cows is also low, estimated at 1.37 liters/cow per day (CSA, 2014). This result in a total annual milk production of 3.81 billion liters and about 50% of this goes to calves Per capita milk consumption is low and stands at 19 kg/year FAO (2011). Therefore, Ethiopia needs to work hard on improving the work of productive and reproductive performance improvements of cattle through appropriate breeding and related activities (CSA, 2006). In spite, of the presence of large and diverse animal genetic resources, the productivity (meat and milk) of livestock remains low in many developing countries including Ethiopia for various reasons, such as inadequate nutrition, poor genetic potential, inadequate animal health services and other management related problems (Lobago, 2007). Cattle breeding are mostly uncontrolled in Ethiopia making genetic improvement difficult and an appropriate bull selection criteria have not yet been established applied and controlled which makes genetic improvement difficult (Webb,2003; Abraham ,2014). Given the considerable potential for smallholder income and employment generation from high-value dairy products, development of the dairy sector can contribute significantly to food security and nutrition of the country (Desalegn et al., 2009). On the other hand, artificial insemination (AI), the most commonly used and valuable biotechnology has been in operation in Ethiopia for over 30 years. Nevertheless, the efficiency and impact of the AI operation has not been well-documented (Engida, 2012). This paper is review status of reproductive technology to improved ruminant production in Ethiopia.

Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine.

Our knowledge of pluripotent stem cell (PSC) biology has advanced to the point where we now can generate most cells of the human body in the laboratory. PSC-derived cardiomyocytes can be generated routinely with high yield and purity for disease research and drug development, and these cells are now gradually entering the clinical research phase for the testing of heart regeneration therapies. However, a major hurdle for their applications is the immature state of these cardiomyocytes. In this Review, we describe the structural and functional properties of cardiomyocytes and present the current approaches to mature PSC-derived cardiomyocytes. To date, the greatest success in maturation of PSC-derived cardiomyocytes has been with transplantation into the heart in animal models and the engineering of 3D heart tissues withelectromechanical conditioning. In conventional 2D cell culture, biophysical stimuli such as mechanical loading, electrical stimulation and nanotopology cues all induce substantial maturation, particularly of the contractile cytoskeleton. Metabolism has emerged as a potent means to control maturation with unexpected effects on electrical and mechanical function. Different interventions induce distinct facets of maturation, suggesting that activating multiple signalling networks might lead to increased maturation. Despite considerable progress, we are still far from being able to generate PSC-derived cardiomyocytes with adult-like phenotypes in vitro. Future progress will come from identifying the developmental drivers of maturation and leveraging them to create more mature cardiomyocytes for research and regenerative medicine.

The Role of Cellular Biology in Maxilo-facial Surgery and Protective Restorations

The essential characteristics of contemporary dental medicine are the precision, avant-garde, technologization and successful clinical purpose of cell therapy with the prospect of further application in the clinical practice of cell therapy methods and other performance methods based on the knowledge of cell biology and regenerative medicine in full function ; despite the very different environments, such teeth can develop normal in adult jaw; thus, if suitable cells can be found that, by combination, produce immature teeth, there is the potential for bio- teeth to become a clinical reality .The maxillary frontal area represents the most important area of the maxillae from an aesthetic point of view and the prosthetic restoration of this area is of primary interest in ensuring the appearance, phonation, incision, in human communication and in the structuring of the individual personality. Affecting the maxillary frontal area or through coronary destruction consecutive cavities and their complications, discolouration, dental malpositions disgraceful or due to lack of dental periodontal units creates problem in the aesthetic prosthetics. These changes existing at the front arcade level cause major disturbances to the physiognomy, to the phonation. In the Clinic of Oral and Maxillofacial Surgery, in a period of 2 years, between 2016 and 2018, we noticed, solved and followed a number of 129 cases; 57 patients-lot endodontic and surgical therapy study; 72 patients, study group prosthetic restorations. Due to the functional role that the maxillary front teeth play, the corrections have to be made within the limits of functional tolerance that fall within the normal occlusal parameters because the functional disturbances dictated only by the aesthetics are not tolerated and can lead to large imbalances. The complex oral rehabilitation of the different clinical cases encountered in the dental practice is largely a challenge for the dentist due to the high degree of different affect but present on all the elements of the system. Keywords: cell therapy method , regenerative medicine, prosthetic restoration

Modeling and analysis of the firefly luciferase reaction and the G-protein coupled receptor signaling pathway with ordinary differential equations increases self confidence in mathematical cell biology for novice graduate students

The push for mathematics and computation in biology is greater than ever before. However, perceptions among biology students on the difficulty of mathematics and programming are a barrier to their implementation. A teaching module introducing quantitative skills to biology students is needed. We implemented modeling of firefly luciferase and G-protein coupled receptor signaling with ordinary differential equations in a course for novice graduate students. We assessed whether the course helped the students increase self confidence in application of mathematics in biology. Two concept inventories tracked learning gains in both general and cell biology knowledge. Pre- and post-semester surveys quantified changes in student confidence and their opinions of the usefulness of these techniques in cell biology. We found that the modeling and analysis activities appeared to improve self confidence in and appreciation of quantitative mathematical biology techniques. We describe our assessment methods to determine the suitability of our module.

Non-proliferative neurogenesis in human periodontal ligament stem cells

Understanding the sequence of events from undifferentiated stem cells to neuron is not only important for the basic knowledge of stem cell biology, but also for therapeutic applications. In this study we examined the sequence of biological events during neural differentiation of human periodontal ligament stem cells (hPDLSCs). Here, we show that hPDLSCs-derived neural-like cells display a sequence of morphologic development highly similar to those reported before in primary neuronal cultures derived from rodent brains. We observed that cell proliferation is not present through neurogenesis from hPDLSCs. Futhermore, we may have discovered micronuclei movement and transient cell nuclei lobulation coincident to in vitro neurogenesis. Morphological analysis also reveals that neurogenic niches in the adult mouse brain contain cells with nuclear shapes highly similar to those observed during in vitro neurogenesis from hPDLSCs. Our results provide additional evidence that it is possible to differentiate hPDLSCs to neuron-like cells and suggest the possibility that the sequence of events from stem cell to neuron does not necessarily requires cell division from stem cell.

SLAM-SAP-Fyn: Old Players with New Roles in iNKT Cell Development and Function.

Invariant natural killer T (iNKT) cells are a unique T cell lineage that develop in the thymus and emerge with a memory-like phenotype. Accordingly, following antigenic stimulation, they can rapidly produce copious amounts of Th1 and Th2 cytokines and mediate activation of several immune cells. Thus, it is not surprising that iNKT cells play diverse roles in a broad range of diseases. Given their pivotal roles in host immunity, it is crucial that we understand the mechanisms that govern iNKT cell development and effector functions. Over the last two decades, several studies have contributed to the current knowledge of iNKT cell biology and activity. Collectively, these studies reveal that the thymic development of iNKT cells, their lineage expansion, and functional properties are tightly regulated by a complex network of transcription factors and signaling molecules. While prior studies have clearly established the importance of the SLAM-SAP-Fyn signaling axis in iNKT cell ontogenesis, recent studies provide exciting mechanistic insights into the role of this signaling cascade in iNKT cell development, lineage fate decisions, and functions. Here we summarize the previous literature and discuss the more recent studies that guide our understanding of iNKT cell development and functional responses.