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:Six decades have passed since the foundational recognition of the primary properties of the stem cells. Research on stem cells has since remained at the forefront of efforts to combat a spectrum of diseases, most notably cancer. Despite remarkable progress in medical science, a definitive cure for cancer has remained elusive, spurring the pursuit of diverse therapeutic strategies, among which stem cell therapy is a particularly promising avenue. Moreover, the utilization of cancer stem cells as a therapeutic source holds immense potential for addressing intractable diseases. The strategy of targeting cancer stem cells is beset with challenges, including immune rejection and disease relapse. Additionally, the capacity to inadvertently generate cancer stem cells upon transplantation underscores the critical need to eliminate these cells to ensure the efficacy of cell-based therapies. This paper underscores the pivotal role of cancer stem cells in onco-therapeutics and their potential to aid in early cancer diagnosis. With the proliferation of tissue banks and their collection of malignant tissue types, a renewable source of medications to combat cancer is on the horizon. While cancer stem cell-based therapy presents sophisticated and significant challenges, it offers unprecedented opportunities to extend human life. Continued technological advancements in stem cell therapy promise to provide new insights and refine approaches for cancer treatment, ushering in a new era of hope and innovation in the fight against this formidable disease.
Project description:Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by the gradual destruction of small intrahepatic bile ducts that eventually leads to liver cirrhosis, failure, and even carcinoma. The treatment options for PBC are limited, and the main treatment choices are the US Food and Drug Administration-approved ursodeoxycholic acid and obeticholic acid. However, many patients fail to respond adequately to these drugs and the adverse effects frequently lead to low life quality. For patients with end-stage PBC, liver transplantation remains the only effective treatment. Given their low immunogenicity, prominent immunomodulation property, differentiation potential, and tissue maintenance capacity, mesenchymal stem cells (MSCs) are emerging as new options for treating liver diseases, including PBC. Accumulating evidence from basic research to clinical studies supports the positive effects of MSC-based therapy for treating PBC. In this review, we characterized the underlying roles and mechanisms of MSCs for treating liver diseases and highlight recent basic and clinical advances in MSC-based therapy for treating PBC. Finally, the current challenges and perspectives for MSC-based therapy in clinical application are discussed, which could help accelerate the application of MSCs in clinical practice, especially for refractory diseases such as PBC.
Project description:Mesenchymal stem cells (MSCs) from multiple tissues have the capability of multidirectional differentiation and self-renewal. Many reports indicated that MSCs exert curative effects on a variety of age-related diseases through regeneration and repair of aging cells and organs. However, as research has progressed, it has become clear that it is the MSCs derived exosomes (MSC-Exos) that may have a real role to play, and that they can be modified to achieve better therapeutic results, making them even more advantageous than MSCs for treating disease. This review generalizes the biological characteristics of MSCs and exosomes and their mechanisms in treating age-related diseases, for example, MSCs and their exosomes can treat age-related diseases through mechanisms such as oxidative stress (OS), Wnt/β-catenin signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and so on. In addition, current in vivo and in vitro trials are described, and ongoing clinical trials are discussed, as well as the prospects and challenges for the future use of exosomes in disease treatment. This review will provide references for using exosomes to treat age-related diseases.
Project description:Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.
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: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.