Stem Cell-based Medicine Research Articles

Microfluidics-assisted Tumor Cell Separation Approaches for Clinical Applications: An Overview on Emerging Devices.

Recent advances in science and technology have led to revolutions in many different scientific and industrial fields. The term lab on a chip, or in other word, performing a variety of complex analyzes in just a short time and in a very small space, is a term that has become very common in recent years, and what used to be a dream has now come to life in practice. In this paper, we has been tried to investigate a specific type of lab technology on a chip, which is of course one of the most common, namely the knowledge and technology of cell separation by using microfluidic technique that can be separated based on size and deformation, adhesion and electrical properties. The tissue of the human body is degraded due to injury or aging, which is often tried to treat this tissue disorder by using drugs, but they are not always enough. Stem cell-based medicine is a novel form of medicine which promises the restoration or regeneration of tissues and functioning organs. Although many models of microfluidic systems have been designed for cell separation, the choice of appropriate device to achieve a reliable result is presented as a challenge. So, in this study, Fluorescence Activated Cell Sorting (FACS), Dielectrophoresis (DEP), Magnetic Activated Cell Sorting (MACS) and Acoustic microfluidic system are four distinct categories of active microfluidic systems explored. Also, the advantages, disadvantages and the current status of the mentioned devices in these methods, are reviewed.

Stem Cells: The Game Changers of Human Cardiac Disease Modelling and Regenerative Medicine.

A comprehensive understanding of the molecular basis and mechanisms underlying cardiac diseases is mandatory for the development of new and effective therapeutic strategies. The lack of appropriate in vitro cell models that faithfully mirror the human disease phenotypes has hampered the understanding of molecular insights responsible of heart injury and disease development. Over the past decade, important scientific advances have revolutionized the field of stem cell biology through the remarkable discovery of reprogramming somatic cells into induced pluripotent stem cells (iPSCs). These advances allowed to achieve the long-standing ambition of modelling human disease in a dish and, more interestingly, paved the way for unprecedented opportunities to translate bench discoveries into new therapies and to come closer to a real and effective stem cell-based medicine. The possibility to generate patient-specific iPSCs, together with the new advances in stem cell differentiation procedures and the availability of novel gene editing approaches and tissue engineering, has proven to be a powerful combination for the generation of phenotypically complex, pluripotent stem cell-based cellular disease models with potential use for early diagnosis, drug screening, and personalized therapy. This review will focus on recent progress and future outcome of iPSCs technology toward a customized medicine and new therapeutic options.

Embodied values: post-pharmaceutical health and the accumulation of surplus vitality in regenerative stem cell medicine

Abstract This paper analyzes an emerging form of post-pharmaceutical health and its underlying regime of value in the global bioeconomy of regenerative stem cell-based medicine (RSCM). Animated by a vision to overcome drug-based therapies and their underlying political economies, RSCM pursues a form of regenerative health that is strikingly at odds with pharmaceutical regimes of drug research, regulation and therapy. To offer a theoretical account of these competing forms of health, the paper provides an analysis of the regimes of values that underpin pharmaceutical and regenerative health respectively. This analysis is done alongside three dimensions: the interlinkage between knowledge, technology and economic value creation; its relation to normative values and ethics; and conceptions and valuations of the biomedical subject and his/her body in biomedical research, intervention and innovation. Contrasting these two diverging regimes of health and value suggests that in RSCM the pharmaceutical logic of accumulating “surplus health” is not entirely dismissed but re-articulated in a regime based on the (re-)generation of regenerative biovalue through the extraction and ex vivo accumulation of “surplus vitality”. Finally, the article discusses “post-pharmaceutical health” as a sensitizing concept that offers new research avenues into emergent forms of health, value, and subjectivity beyond RSCM.

Multifunctional Photo- and Magnetoresponsive Graphene Oxide-Fe3O4 Nanocomposite-Alginate Hydrogel Platform for Ice Recrystallization Inhibition.

Tuning ice recrystallization (IR) has attracted tremendous interest in fundamental research and a variety of practical applications, including food and pharmaceutical engineering, fabrication of anti-icing coating and porous materials, and cryopreservation of biological cells and tissues. Although great efforts have been devoted to modulation of IR for better microstructure control of various materials, it still remains a challenge, especially in cryopreservation, where insufficient suppression of IR during warming is fatal to the cells. Herein, we report an all-in-one platform, combining the external physical fields and the functional materials for both active and passive suppression of IR, where the photo- and magnetothermal dual-modal heating of GO-Fe3O4 nanocomposites (NCs) can be used to suppress IR with both enhanced global warming and microscale thermal disturbance. Moreover, the materials alginate hydrogels and GO-Fe3O4 NCs can act as IR inhibitors for further suppression of the IR effect. As a typical application, we show that this GO-Fe3O4 nanocomposite-alginate hydrogel platform can successfully enable low-cryoprotectant, high-quality vitrification of stem cell-laden hydrogels. We believe that the versatile ice recrystallization inhibition platform will have a profound influence on cryopreservation and tremendously facilitate stem cell-based medicine to meet its ever-increasing demand in clinical settings.

Stem and Progenitor Cells in thePathogenesis and Treatment of Digestive Diseases.

The global epidemic of chronic degenerative diseases expands rapidly. The pathogenesis of these noncommunicable disorders revolves around innate immunity, microbiome, and stem cell alterations. Understanding the mechanisms behind stem cell biology and their regulatory pathways is a key to understanding the origin of human disease. Stem cells are involved in tissue and organ damage and regeneration. The evidence is mounting that not only eukaryotic cells but also gut microbiota may release extracellular microvesicles that are absorbed from the gut into the portal and systemic circulation. Linking the fields of stem cells, innate immunity and microbiome research opens up new avenues to develop novel diagnostic (e.g., biomarkers), therapeutic (e.g., microbiome modulation, stem cell-based medicines), and prognostic (personalized diets) tools. In this chapter, we present the short overview of various stem and progenitor cells of adult tissues circulating in peripheral blood and their role in the pathogenesis and treatment of digestive diseases. We also briefly discuss the role of host-stem cell-microbial interactions as a new frontier of research in gastroenterology.

Concise review: custodians of the transcriptome: how microRNAs guard stemness in squamous epithelia.

At the core of every dynamic epithelium resides a population of carefully regulated stem cells ensuring its maintenance and balance. The complex mammalian epidermis is no exception to this rule. The last decade has delivered a wealth of knowledge regarding the biology of adult stem cells, but questions still remain regarding the intricate details of their function and maintenance. To help address these gaps, we turn to the small, single-stranded RNA molecules known as microRNAs. Since their discovery, microRNAs have provided us with novel insights and ground-breaking impulses to enhance our understanding of the biological sciences. Due to their unique role in post-transcriptional regulation, microRNAs are essential to cutaneous biology as well as the epidermal stem cell. By serving as buffers to balance between epithelial stemness, proliferation, and differentiation, microRNAs play essential roles in the maintenance of cutaneous stem cells and their transition out of the stem cell compartment. Following an updated overview of microRNA biology, we summarize the current knowledge of the role of microRNAs in cutaneous stem cells, focusing on three major players that have dominated the recent literature: miR-205, miR-203, and miR-125b. We then review clinical applications, discussing the potential of microRNAs as therapeutic targets in regenerative and oncological stem cell-based medicine.

Use of human embryonic stem cells and umbilical cord blood stem cells for research and therapy: a prospective survey among health care professionals and patients in Switzerland

Scientific progress in the biology of hematopoietic stem cells (HSCs) provides opportunities for advances in therapy for different diseases. While stem cell sources such as umbilical cord blood (UCB) are unproblematic, other sources such as human embryonic stem cells (hESCs) raise ethical concerns. In a prospective survey we established the ethical acceptability of collection, research, and therapy with UCB HSCs versus hESCs among health care professionals, pregnant women, patients undergoing in vitro fertilization therapy, parents, and HSC donors and recipients in Switzerland. There was overall agreement about an ethical justification for the collection of UCB for research and therapy in the majority of participants (82%). In contrast, research and therapy with hESCs was acceptable only by a minority (38% of all responders). The collection of hESCs solely created for HSC collection purposes met overall with the lowest approval rates. Hematologists displayed among the participants the highest acceptance rates for the use of hESCs with 55% for collection, 63% for research, and 73% for therapy. This is the first study assessing the perception of hESCs for research and therapy in comparison with UCB HSCs in different target groups that are exposed directly, indirectly, or not at all to stem cell-based medicine. Our study shows that the debate over the legitimacy of embryo-destructive transplantation medicine is far from over as particularly hESC research continues to present an ethical problem to an overwhelming majority among laypersons and even among health care professionals.

Myocardial cell sheet therapy and cardiac function

Heart failure (HF) is the leading cause of death in developed countries. Regenerative medicine has the potential to drastically improve treatment for advanced HF. Stem cell-based medicine has received attention as a promising candidate therapy over the past decade; however, it has not yet realized this potential in terms of reliability. The cell sheet is an innovative technology for constructing aligned graft cells, and several cell sources have been investigated for making a feasible cell sheet. The most representative thus far is skeletal myoblast, although such cells raise the issue of arrhythmogenicity. Regenerative cardiomyocytes (CMs) derived from pluripotent stem cells (PSCs), such as embryonic stem cells or induced PSCs, are the most promising, because a myocardial cell sheet (MCS) constructed with regenerative CMs can potentially enable contraction recovery and electromechanical coupling with host CMs. The functional outcomes of experimental MCS are reduction of ventricular wall stress and paracrine effects rather than contraction recovery. Several technical obstacles still hamper the clinical application of MCSs, with graft survival the most pivotal issue. Ischemia, apoptosis, inflammation, and immune response can all cause graft cell death, and a stable blood supply to the MCS is critical for successful engraftment. Ventricular tachycardia must also be considered in any myocardial cell therapy, and multiple layering of MCS (>3 layers) is necessary to reconstruct human myocardium. Innervation is also a potential issue. The future application of myocardial cell therapy with MCS for advanced HF depends on resolving these difficulties.

Concise Review: Managing Genotoxicity in the Therapeutic Modification of Stem Cells

The therapeutic use of procedures for genetic stem cell modification is limited by potential adverse events related to uncontrolled mutagenesis. Prominent findings have been made in hematopoietic gene therapy, demonstrating the risk of clonal, potentially malignant outgrowth on the basis of mutations acquired during or after therapeutic genome modification. The incidence and the growth rate of insertional mutants have been linked to the "stemness" of the target cells and vector-related features such as the integration pattern, the architecture, and the exact content of transgene cassettes. Milieu factors supporting the survival and expansion of mutants may eventually allow oncogenic progression. Similar concerns apply for medicinal products based on pluripotent stem cells. Focusing on the genetic stress induced by insertional mutagenesis and culture adaptation, we propose four conclusions. (a) Mutations occurring in the production of stem cell-based medicines may be unavoidable and need to be classified according to their risk to trigger the formation of clones that are sufficiently long-lived and mitotically active to acquire secondary transforming mutations. (b) The development of rational prevention strategies depends upon the identification of the specific mutations forming such "dominant clones" (which can also be addressed as cancer stem cell precursors) and a better knowledge of the mechanisms underlying their creation, expansion, and homeostatic control. (c) Quantitative assay systems are required to assess the practical value of preventive actions. (d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants.

Pharma's Developing Interest in Stem Cells

Human stem cell biology is driving the promise of novel regenerative therapies into clinical trials. Although the pharmaceutical industry has embraced stem cells as tools in drug discovery, few companies have taken the risk to deliver stem cell-based medicines. Here, we evaluate the various cell-based opportunities and corporate strategies.