Project description:Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, and subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting vascular regeneration and the release neuro-nutrients, and are a promising strategy for the treatment of SCI. Preclinical studies have shown that MSCs promote sensory and motor function recovery in rats. In clinical trials, MSCs have been reported to improve the American Spinal Injury Association (ASIA) sensory and motor scores. However, the effectiveness of MSCs in treating patients with SCI remains controversial. MSCs promote tumorigenesis and ensuring the survival of MSCs in the hostile environment of SCI is challenging. In this article we examine the evidence on the pathophysiological changes occurring after SCI. We then review the underlying mechanisms of MSCs in the treatment of SCI and summarize the potential application of MSCs in clinical practice. Finally, we highlight the challenges surrounding the use of MSCs in the treatment of SCI and discuss future applications.
Project description:Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.
Project description:Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence. This has led to further expansion in clinical indications from graft rejection, autoimmune diseases, and osteoarthritis, to inflammatory liver and pulmonary diseases including COVID-19. A clear trend is the shift from using autologous to allogeneic MSCs, which can be immediately available as off-the-shelf products. In addition, new products such as cell-free exosomes and human pluripotent stem cell (hPSC)-derived MSCs are exciting developments to further prevalent use. Increasing numbers of trials have now published results in which safety of MSCT has been largely demonstrated. While reports of therapeutic endpoints are still emerging, efficacy can be seen for specific indications-including graft-vs-host-disease, strongly Th17-mediated autoimmune diseases, and osteoarthritis-which are more robustly supported by mechanistic preclinical evidence. In this review, we update and discuss outcomes in current MSCT clinical trials for immune and inflammatory disease, as well as new innovation and emerging trends in the field.
Project description:Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.
Project description:Tuberculosis (TB) is one of the communicable diseases caused by Mycobacterium tuberculosis (Mtb) infection, affecting nearly one-third of the world's population. However, because the pathogenesis of TB is still not fully understood and the development of anti-TB drug is slow, TB remains a global public health problem. In recent years, with the gradual discovery and confirmation of the immunomodulatory properties of mesenchymal stem cells (MSCs), more and more studies, including our team's research, have shown that MSCs seem to be closely related to the growth status of Mtb and the occurrence and development of TB, which is expected to bring new hope for the clinical treatment of TB. This article reviews the relationship between MSCs and the occurrence and development of TB and the potential application of MSCs in the treatment of TB.
Project description:The cellular and molecular mechanisms responsible for pregnancy-related disorders remain unclear. We investigated the feasibility of using placenta-derived mesenchymal stem cells (MSCs) as a tool to study such pregnancy-related disorders. We isolated and expanded adequate numbers of cells with characteristic features of MSCs from the chorionic plate (CP-MSCs), chorionic villi (CV-MSCs), and decidua basalis (DB-MSCs) of human term placental tissues. All placenta-derived MSCs expressed pregnancy-associated C14MC microRNA (miRNA) (miR-323-3p). Interestingly, the placenta-specific C19MC miRNAs (miR-518b and miR517a) were clearly expressed in CP-MSCs and CV-MSCs of foetal origin, but were barely expressed in DB-MSCs of maternal origin. Furthermore, expression levels of placenta-specific C19MC miRNAs in CV-MSCs remained stable during the ex vivo expansion process and across different pregnancy phases (first trimester versus third trimester). High-efficiency siRNA transfection was confirmed in twice-passaged CV-MSCs with little toxicity, and microarray analysis was used to screen for miR-518b target genes. Placenta-derived MSCs, especially CV-MSCs, are a potential tool for investigating the role of placental miRNAs in pregnancy-related disorders.
Project description:Mesenchymal stem cells (MSCs) are multipotent stem cells that have multilinear differentiation and self-renewal abilities. These cells are immune-privileged as they express no or low level of class-II major histocompatibility complex (MHC-II) and other costimulatory molecules. Having neuroprotective and regenerative properties, MSCs can be used to ameliorate several intractable neurodegenerative disorders by affecting both innate and adaptive immune systems. Several manipulations like pretreating MSCs with different conditions or agents, and using molecules derived from MSCs or genetically manipulating them, are the common and practical ways that can be used to strengthen MSCs survival and potency. Improved MSCs can have significantly enhanced impacts on diseases compared to MSCs not manipulated. In this review, we describe some of the most important manipulations that have been exerted on MSCs to improve their therapeutic functions and their applications in ameliorating three prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.
Project description:Stem cell therapy is a promising alternative approach to heart diseases. The most prevalent source of multipotent stem cells, usually called somatic or adult stem cells (mesenchymal stromal/stem cells, MSCs) used in clinical trials is bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs) and placenta. Therapeutic use of MSCs in cardiovascular diseases is based on the benefits in reducing cardiac fibrosis and inflammation that compose the cardiac remodeling responsible for the maintenance of normal function, something which may end up causing progressive and irreversible dysfunction. Many factors lead to cardiac fibrosis and failure, and an effective therapy is lacking to reverse or attenuate this condition. Different approaches have been shown to be promising in surpassing the poor survival of transplanted cells in cardiac tissue to provide cardioprotection and prevent cardiac remodeling. This review includes the description of pre-clinical and clinical investigation of the therapeutic potential of MSCs in improving ventricular dysfunction consequent to diverse cardiac diseases.
Project description:Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor cells with demonstrated ability for tumor growth, invasion, metastasis, and resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive yet elusive therapeutic option, with the goal of increasing specificity and effectiveness in tumor eradication, as well as decreasing off-target or systemic toxicity. Research into further characterization and targeted therapy toward head and neck CSCs is an active and rapidly evolving field. This review discusses the current state of research into therapy against head and neck CSCs and future directions for targeted therapy.