Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

GMP-Based Isolation of Full-Term Human Placenta-Derived NK Cells for CAR-NK Cell Therapy in Malignant Melanoma.

Melanoma, a severe type of skin cancer, poses significant management challenges due to its resistance to available treatments. Despite this obstacle, the high immunogenicity of melanoma renders it amenable to immune therapy, and NK cells have been identified as possessing anti-tumor properties in immunotherapy. The development of chimeric antigen receptor (CAR)-modified NK cells, or CAR-NK cells, has shown potential in enhancing immunotherapeutic regimens. To achieve this, researchers have explored various sources of NK cells, including those derived from the placenta, which offers benefits compared to other sources due to their limited ex vivo expansion potential. Recent studies have indicated the capacity to expand functional NK cells from placenta-derived cells in vitro that possess anti-tumor cytolytic properties. This chapter discusses the isolation of full-term human placenta-derived NK cells using Good Manufacturing Practice-based methods for CAR-NK cell therapy in melanoma.

Application of Biocompatible Scaffolds in Stem-Cell-Based Dental Tissue Engineering.

Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.

Potential for Stem Cell-Based Therapy in the Road of Treatment for Neurological Disorders Secondary to COVID-19.

Abstract: The severe acute respiratory syndrome coronavirus 2 has led to the worldwide pandemic named coronavirus disease 2019 (COVID-19). It has caused a significant increase in the number of cases and mortalities since its first diagnosis in December 2019. Although COVID-19 primarily affects the respiratory system, neurological involvement of the central and peripheral nervous system has been also reported. Herein, the higher risk of neurodegenerative diseases in COVID-19 patients in future is also imaginable. Neurological complications of COVID-19 infection are more commonly seen in severely ill individuals; but, earlier diagnosis and treatment can lead to better long-lasting results. In this respect, stem cell biotechnologies with considerable self-renewal and differentiation capacities have experienced great progress in the field of neurological disorders whether in finding out their underlying processes or proving them promising therapeutic approaches. Herein, many neurological disorders have been found to benefit from stem cell medicine strategies. Accordingly, in the present review, the authors are trying to discuss stem cell-based biotechnologies as promising therapeutic options for neurological disorders secondary to COVID-19 infection through reviewing neurological manifestations of COVID-19 and current stem cell-based biotechnologies for neurological disorders. Lay Summary: Due to the substantial burden of neurological disorders in the health, economic, and social system of society, the emergence of neurological manifestations following COVID-19 (as a life-threatening pandemic) creates the need to use efficient and modern methods of treatment. Since stem cell-based methods have been efficient for a large number of neurological diseases, it seems that the use of mentioned methods is also effective in the process of improving neurological disorders caused by COVID-19. Hereupon, the current review aims to address stem cell-based approaches as treatments showing promise to neurological disorders related to COVID-19.

Regenerative Medicine for the Treatment of Ischemic Heart Disease; Status and Future Perspectives.

Cardiovascular disease is now the leading cause of adult death in the world. According to new estimates from the World Health Organization, myocardial infarction (MI) is responsible for four out of every five deaths due to cardiovascular disease. Conventional treatments of MI are taking aspirin and nitroglycerin as intermediate treatments and injecting antithrombotic agents within the first 3 h after MI. Coronary artery bypass grafting and percutaneous coronary intervention are the most common long term treatments. Since none of these interventions will fully regenerate the infarcted myocardium, there is value in pursuing more innovative therapeutic approaches. Regenerative medicine is an innovative interdisciplinary method for rebuilding, replacing, or repairing the missed part of different organs in the body, as similar as possible to the primary structure. In recent years, regenerative medicine has been widely utilized as a treatment for ischemic heart disease (one of the most fatal factors around the world) to repair the lost part of the heart by using stem cells. Here, the development of mesenchymal stem cells causes a breakthrough in the treatment of different cardiovascular diseases. They are easily obtainable from different sources, and expanded and enriched easily, with no need for immunosuppressing agents before transplantation, and fewer possibilities of genetic abnormality accompany them through multiple passages. The production of new cardiomyocytes can result from the transplantation of different types of stem cells. Accordingly, due to its remarkable benefits, stem cell therapy has received attention in recent years as it provides a drug-free and surgical treatment for patients and encourages a more safe and feasible cardiac repair. Although different clinical trials have reported on the promising benefits of stem cell therapy, there is still uncertainty about its mechanism of action. It is important to conduct different preclinical and clinical studies to explore the exact mechanism of action of the cells. After reviewing the pathophysiology of MI, this study addresses the role of tissue regeneration using various materials, including different types of stem cells. It proves some appropriate data about the importance of ethical problems, which leads to future perspectives on this scientific method.

Diabetes and Heart Failure: Multi-Omics Approaches.

Diabetes and heart failure, as important global issues, cause substantial expenses to countries and medical systems because of the morbidity and mortality rates. Most people with diabetes suffer from type 2 diabetes, which has an amplifying effect on the prevalence and severity of many health problems such as stroke, neuropathy, retinopathy, kidney injuries, and cardiovascular disease. Type 2 diabetes is one of the cornerstones of heart failure, another health epidemic, with 44% prevalence. Therefore, finding and targeting specific molecular and cellular pathways involved in the pathophysiology of each disease, either in diagnosis or treatment, will be beneficial. For diabetic cardiomyopathy, there are several mechanisms through which clinical heart failure is developed; oxidative stress with mediation of reactive oxygen species (ROS), reduced myocardial perfusion due to endothelial dysfunction, autonomic dysfunction, and metabolic changes, such as impaired glucose levels caused by insulin resistance, are the four main mechanisms. In the field of oxidative stress, advanced glycation end products (AGEs), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are the key mediators that new omics-driven methods can target. Besides, diabetes can affect myocardial function by impairing calcium (Ca) homeostasis, the mechanism in which reduced protein phosphatase 1 (PP1), sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a), and phosphorylated SERCA2a expressions are the main effectors. This article reviewed the recent omics-driven discoveries in the diagnosis and treatment of type 2 diabetes and heart failure with focus on the common molecular mechanisms.

The Outcome of Stem Cell-Based Therapies on the Immune Responses in Rheumatoid Arthritis.

Rheumatoid arthritis as a common autoimmune inflammatory disorder with unknown etiology can affect 0.5-1% of adults in developed countries. It involves more than just the patient's joints and can be accompanied by several comorbidities and affect cardiovascular, pulmonary, and some other systems of the human body. Although cytokine-mediated pathways are mentioned to have a central role in RA pathogenesis, adaptive and innate immune systems and intracellular signaling pathways all have important roles in this process. Non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying anti-rheumatic drugs, and biological agents are some mentioned medications used for RA. They are accompanied by some adverse effects and treatment failures which elucidates the needing for novel and more powerful therapeutic approaches. Stem cell-based therapies and their beneficial effects on therapeutic processes of different diseases have been founded so far. They can be an alternative and promising therapeutic approach for RA, too; due to their effects on immune responses of the disease. This review, besides some explanations about RA characteristics, addresses the outcome of the stem cell-based therapies including mesenchymal stem cell transplantation and hematopoietic stem cell transplantation for RA and explains their effects on the disease improvement.