The wonders of stem cells therapeutic application towards chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by its heterogeneous nature, progressive course, and significant impact on individuals' quality of life. It is a prevalent global health issue affecting a substantial number of individuals and can pose life-threatening complications if left unmanaged. The development and course of COPD can be influenced by a range of risk factors, including genetic predisposition and environmental exposures. Nevertheless, as researchers adopt a more comprehensive and expansive viewpoint of therapeutic techniques, the associated obstacles become more apparent. Indeed, a definitive medication for COPD that reliably leads to symptom alleviation has not yet been discovered. Therefore, the limitations of conventional therapy methods prompted researchers to focus on the advancement of novel procedures, potentially leading to significant outcomes. In contemporary times, the field of regenerative medicine and cell therapy has presented unprecedented opportunities for the exploration of innovative treatments for COPD, owing to the distinctive attributes exhibited by stem cells. Hence, it is imperative to provide due consideration to preclinical investigations and notable characteristics of stem cells as they serve as a means to comprehensively comprehend the fundamental mechanisms of COPD and uncover novel therapeutic strategies with enhanced efficacy for patients.

Brown adipose tissue and alzheimer's disease.

Alzheimer's disease (AD), the most common type of senile dementia, is a chronic neurodegenerative disease characterized by cognitive dysfunction and behavioral disability. The two histopathological hallmarks in this disease are the extraneuronal accumulation of amyloid-ß (Aß) and the intraneuronal deposition of neurofibrillary tangles (NFTs). Despite this, central and peripheral metabolic dysfunction, such as abnormal brain signaling, insulin resistance, inflammation, and impaired glucose utilization, have been indicated to be correlated with AD. There is solid evidence that the age-associated thermoregulatory deficit induces diverse metabolic changes associated with AD development. Brown adipose tissue (BAT) has been known as a thermoregulatory organ particularly vital during infancy. However, in recent years, BAT has been accepted as an endocrine organ, being involved in various functions that prevent AD, such as regulating energy metabolism, secreting hormones, improving insulin sensitivity, and increasing glucose utilization in adult humans. This review focuses on the mechanisms of BAT activation and the effect of aging on BAT production and signaling. Specifically, the evidence demonstrating the effect of BAT on pathological mechanisms influencing the development of AD, including insulin pathway, thermoregulation, and other hormonal pathways, are reviewed in this article.

DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.

Stem cells, as a group of undifferentiated cells, are enriched with self-renewal and high proliferative capacity, which have attracted the attention of many researchers as a promising approach in the treatment of many diseases over the past years. However, from the cellular and molecular point of view, the DNA repair system is one of the biggest challenges in achieving therapeutic goals through stem cell technology. DNA repair mechanisms are an advantage for stem cells that are constantly multiplying to deal with various types of DNA damage. However, this mechanism can be considered a trump card in the game of cell survival and treatment resistance in cancer stem cells, which can hinder the curability of various types of cancer. Therefore, getting a deep insight into the DNA repair system can bring researchers one step closer to achieving major therapeutic goals. The remarkable thing about the DNA repair system is that this system is not only under the control of genetic factors, but also under the control of epigenetic factors. Therefore, it is necessary to investigate the role of the DNA repair system in maintaining the survival of cancer stem cells from both aspects.

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.

How to establish infrastructures to achieve more efficient regenerative medicine?

The field of regenerative medicine (RM) as an innovative technology has the ability to affect the healthcare system. It develops a variety of techniques through stem cell biology, genetics, bioengineering, biomaterial science, and tissue engineering to replace or restore the role of lost, disabled, or aging cells in the human body. However, the field's proficiency has still been underwhelming at the clinical trial level. This could be due to the innovation of such technologies, as well as their incredible nature. Therefore, managing the infrastructure framework for the safe and efficient application of the aforementioned field of science would help in the process of progress. In this context, the current review focuses on how to establish infrastructures for more effective RM.

The Fingerprints of Biomedical Science in Internal Medicine.

With the development of numerous advances in science and technologies, medical science has also been updated. Internal medicine is one of the most valuable specialized fields of medical sciences that review a broad range of diseases. Herein, the internal medicine specialist (internist) is obliged to do diagnostic measures to evaluate disease signs and symptoms. In recent times, biomedical sciences as the new emergence science (including cellular and molecular biology, genetics, nanobiotechnology, bioinformatics, biochemistry, etc.) have been capable of providing more specific diagnostic methods together with techniques for better understanding the mechanism of the disease and the best diseases modeling and offering proper therapies. Accordingly, the authors have tried to review the link between biomedical sciences and medicine, particularly internal medicine.

Metabolomics Signatures of SARS-CoV-2 Infection.

For a very long time, viral infections have been considered as one of the most important causes of death and disability around the world. Through the viral infection, viruses as small pathogens enter the host cells and use hosts' biosynthesis machinery to replicate and collect infectious lineages. Moreover, they can modify hosts' metabolic pathways in order to their own purposes. Nowadays (in 2019-2020), the most famous type of viral infection which was caused by a novel type of coronavirus is called COVID-19 disease. It has claimed the lives of many people around the world and is a very serious threat to health. Since investigations of the effects of viruses on host metabolism using metabolomics tools may have given focuses on novel appropriate treatments, in the current review the authors highlighted the virus-host metabolic interactions and metabolomics perspective in COVID-19.

An Overview of Zebrafish Modeling Methods in Drug Discovery and Development.

Animal studies are recognized as a significant step forward in the bridging between drug discovery and clinical applications. Animal models, due to their relative genetic, molecular, physiological, and even anatomical similarities to humans, can provide a suitable platform for unraveling the mechanisms underlying human diseases and discovering new therapeutic approaches as well. Recently, zebrafish has attracted attention as a valuable experimental and pharmacological model in drug discovery and development studies due to its prominent characteristics such as the high degree of genetic similarity with humans, genetic manipulability, and prominent clinical features. Since advancing a theory to a valid and reliable observation requires the manipulation of animals, it is, therefore, essential to use efficient modeling methods appropriate to the different aspects of experimental conditions. In this context, applying several various approaches such as using chemicals, pathogens, and genetic manipulation approaches allows zebrafish development into a preferable model that mimics some human disease pathophysiology. Thus, such modeling approaches not only can provide a framework for a comprehensive understanding of the human disease mechanisms that have a counterpart in zebrafish but also can pave the way for discovering new drugs that are accompanied by higher amelioration effects on different human diseases.

Looking at time dependent differentiation of mesenchymal stem cells by culture media using MALDI-TOF-MS.

Mesenchymal stem cells (MSCs) are multipotent cells which are popular in human regenerative medicine. These cells can renew themselves and differentiate into several specialized cell types including osteoblasts, adipocytes, and chondrocytes under physiological and experimental conditions. MSCs can secret a lot of components including proteins and metabolites. These components have significant effects on their surrounding cells and also can be used to characterize them. This characterization of multipotent MSCs plays a critical role in their therapeutic potential. The metabolic profile of culture media verified by applying matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques. Also, the differentiation and development of MSCs have monitored through culture media metabolome or secretome (secreted metabolites). Totally, 24 potential metabolites were identified. Between them 12 metabolites are unique to BM-MSCs and 5 metabolites are unique to AD-MSCs. Trilineage differentiation including chondrocytes, osteoblasts, and adipocytes, as well as metabolites that are being differentiated, have been shown in different weeks. In the present study, the therapeutic effects of MSCs analyzed by decoding the metabolome for MSCs secretome via metabolic profiling using MALDI-TOF-MS techniques.

Brown adipose tissue transplantation as a novel alternative to obesity treatment: a systematic review.

BACKGROUND: Obesity, a global challenge, is a complex disorder linked to various diseases. Different kinds of treatments are currently used to treat or control this pandemic. Despite their positive effects on controlling obesity, they still have limitations and side effects including digestive problems, difficulties of daily infusion of some drugs, surgical complications, and weight regain. All these issues cause these conventional methods not to have desirable efficacy. In this regard, brown adipose tissue (BAT) transplantation as a new investigational treatment is proposed, which has beneficial effects with no documented side effect in studies up to now. METHODS: This systematic review protocol was registered in the International Prospective Register of Systematic Reviews (Registration Number: CRD42018110045). The systematical search was conducted on Web of Science, Scopus, PubMed, Embase, and ProQuest databases. The quality assessments in the included studies and data gathering were conducted independently by two authors. The main variables were anthropometric indices including body weight, levels of leptin, IGF-1, glucagon, adiponectin, fasting blood glucose, and UCP-1. RESULTS: Following the search in mentioned databases, ten articles were entered into this systematic review. In most studies, weight gain and white adipocyte size were reduced in the BAT transplant group. It seems that the transplantation leads to the regeneration of healthy adipose tissue by activating the endogenous BAT. CONCLUSIONS: Since BAT transplantation is one of the possible future treatments of obesity, many studies are conducted to evaluate the outcomes and related procedures precisely, so it can finally step into clinical application.

Cellular therapy for treatment of spinal cord injury in Zebrafish model.

Spinal cord injury is a serious problem with a high rate of morbidity and mortality for all persons, especially young people (15-25 years old). Due to the large burden and the costs incurred on the government, finding the best therapeutic approach is necessary. In this respect, treatment strategies based on the disease mechanism can be effective. After the first trauma of spinal cord cascades, cellular events happen one after the other known as secondary trauma. The mechanism of secondary events of spinal cord injury could be helpful for target therapy as trying to stop the secondary trauma. Herein, some medical and surgical therapy has been introduced and cell therapy strategy was considered as a recent method. Actually, cell therapy is defined as the application of different cells including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and some others to replace or reconstruct the damaged tissues and restore their functions. However, as a newly emerged therapeutic method, cell therapy should be used through various subclinical studies in animal models to assess the efficacy of the treatment under controlled conditions. In this review, the role of Zebrafish as a recommended model has been discussed and combinatory approach as the probably most useful treatment has been suggested.

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.

The Design and Application of an Appropriate Parkinson's Disease Animal Model in Regenerative Medicine.

OBJECTIVES: Aging as an inevitable and complex physiological process occurs through a progressive decrease in the potential of tissue regeneration. Given the increasing global outbreak of aging and age-related disorders, it is important to control this phenomenon. Parkinson's disease (one of the age-related neurodegenerative and progressive disorders) resulted from predominant dopaminergic neurons deficiency. Usual Parkinson's disease treatments just can lead to symptomatically relieving. Recently, cell therapy and regenerative medicine a great promise in the treatment of several types of disorders including Parkinson's disease. Herein, before starting clinical trials, preclinical studies should be performed to answer some fundamental questions about the safety and efficacy of various treatments. Additionally, developing a well-designed and approved study is required to provide an appropriate animal model with strongly reliable validation methods. Hereupon, this review will discuss about the design and application of an appropriate Parkinson's disease animal model in regenerative medicine. EVIDENCE ACQUISITION: In order to conduct the present review, numbers of Parkinson's disease preclinical studies, as well as literatures related to the animal modeling, were considered. RESULTS: Appropriate animal models which approved by related authorize committees should have a high similarity to humans from anatomical, physiological, behavioral, and genetic characteristics view of point. CONCLUSION: It is concluded that animal studies before starting clinical trials have an important role in answering the crucial questions about the various treatments safety and efficacy. Therein, it is recommended that all of animal modeling stages be assessed by animal ethics and welfare guidelines and also evaluated by different validation tests. However, it is better to find some alternatives to replacement, refinement, and, reduction of animals. Nowadays, some novel technologies such as using imaging methods have been introduced.

Opportunities and Challenges in Stem Cell Aging.

Studying aging, as a physiological process that can cause various pathological phenotypes, has attracted lots of attention due to its increasing burden and prevalence. Therefore, understanding its mechanism to find novel therapeutic alternatives for age-related disorders such as neurodegenerative and cardiovascular diseases is essential. Stem cell senescence plays an important role in aging. In the context of the underlying pathways, mitochondrial dysfunction, epigenetic and genetic alterations, and other mechanisms have been studied and as a consequence, several rejuvenation strategies targeting these mechanisms like pharmaceutical interventions, genetic modification, and cellular reprogramming have been proposed. On the other hand, since stem cells have great potential for disease modeling, they have been useful for representing aging and its associated disorders. Accordingly, the main mechanisms of senescence in stem cells and promising ways of rejuvenation, along with some examples of stem cell models for aging are introduced and discussed. This review aims to prepare a comprehensive summary of the findings by focusing on the most recent ones to shine a light on this area of research.

Cellular Dust as a Novel Hope for Regenerative Cancer Medicine.

Although stem cells have the most therapeutic potential, the advantages of regenerative medicine may be best provided using extracellular vesicles which also known in the past as "cellular dust." These microparticles are substances released by cells and play a pivotal role in pathophysiology of tumor progression and metastasis, thrombosis, and inflammation. Extracellular vesicles including exosomes and cell-derived microparticles supporting many physiological and disease processes which are relevant to immunology, hemostasis, thrombosis, neurobiology, cell signaling, angiogenesis, and cancer. While they have not any value for many years, this cellular dust has been studied and shows therapeutic properties similar to their mother cells (stem cells) but without their disadvantages. These vesicles do not divide, limiting the risk of cancer, and do not differentiate either. Therefore, they prevent tumor progression and development of poor function. Furthermore, it appears that they can be produced by a single donor for several patients, and have already confirmed their therapeutic potential in animals in repairing heart, liver and kidney lesions. The present study was aimed to introduce cellular dust as a new horizon for regenerative cancer medicine and also new hope for potential therapeutic applications of cancer and associated diseases.

Therapeutic abortion and ectopic pregnancy: alternative sources for fetal stem cell research and therapy in Iran as an Islamic country.

Regenerative medicine as a background of stem cell research and therapy has a long history. A wide variety of diseases including Parkinson's disease, heart diseases, multiple sclerosis, spinal cord injury, diabetes mellitus and etc. are candidate to be treated using different types of stem cells. There are several sources of stem cells such as bone marrow, umbilical cord, peripheral blood, germ cells and the embryo/fetus tissues. Fetal stem cells (FSCs) and embryonic stem cells (ESCs) have been described as the most potent stem cell source. Although their pluri- or multipotent properties leads to promising reports for their clinical applications, owning to some ethical and legal obstacles in different communities such as Muslim countries, care should be taken for therapeutic applications of FSCs and ESCs. Derivation of these cell types needs termination of pregnancy and embryo or fetus life that is prohibited according to almost all rules and teaches in Muslim communities. Abortion and termination of pregnancy under a normal condition for the procurement of stem cell materials is forbidden by nearly all the major world religions such as Islam. Legislated laws in the most of Muslim countries permit termination of pregnancy and abortion only when the life of the mother is severely threatened or when continuing pregnancy may lead to the birth of a mentally retarded, genetically or anatomically malformed child. Based on the rules and conditions in Islamic countries, finding an alternative and biologically normal source for embryonic or fetal stem cell isolation will be too difficult. On the one hand, Muslim scientists have the feasibility for finding of genetically and anatomically normal embryonic or fetal stem cell sources for research or therapy, but on the other hand they should adhere to the law and related regional and local rules in all parts of their investigation. The authors suggest that the utilization of ectopic pregnancy (EP) conceptus, extra-embryonic tissues, and therapeutic abortion materials as a valuable source of stem cells for research and medical purposes can overcome limitations associated with finding the appropriate stem cell source. Pregnancy termination because of the mentioned subjects is accepted by almost all Islamic laws because of maternal lifesaving. Also, there are no ethical or legal obstacles in the use of extra-embryonic or EP derived tissues which lead to candidate FSCs as a valuable source for stem cell researches and therapeutic applications.

Mesenchymal Stem Cells-Derived Exosomes for Wound Regeneration.

Wound healing is a complex process with the considerable burden on healthcare system. There are several cellular therapy methods that have been introduced to treat different types of wounds. Despite the advantages of cellular therapy, it is needed to overcome different limitations of this method such as; tumorigenicity and immune rejection. Accordingly, scientists have suggested cell-based vesicles and exosomes. Exosomes can promote proliferation, migration, and angiogenesis process in the wound environment. They have also some advantages such as the potential for drug and gene delivery, easy to storage, and stability in the body. These advantages make them as a novel approach in regenerative medicine without the limitations of cellular therapy. In this review, the authors emphasize on biological properties of MSC-exosomes and their therapeutic effects as a new strategy for wound regeneration.

Tissue Engineered Skin Substitutes.

The fundamental skin role is to supply a supportive barrier to protect body against harmful agents and injuries. Three layers of skin including epidermis, dermis and hypodermis form a sophisticated tissue composed of extracellular matrix (ECM) mainly made of collagens and glycosaminoglycans (GAGs) as a scaffold, different cell types such as keratinocytes, fibroblasts and functional cells embedded in the ECM. When the skin is injured, depends on its severity, the majority of mentioned components are recruited to wound regeneration. Additionally, different growth factors like fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) are needed to orchestrated wound healing process. In case of large surface area wounds, natural wound repair seems inefficient. Inspired by nature, scientists in tissue engineering field attempt to engineered constructs mimicking natural healing process to promote skin restoration in untreatable injuries. There are three main types of commercially available engineered skin substitutes including epidermal, dermal, and dermoepidermal. Each of them could be composed of scaffold, desired cell types or growth factors. These substitutes could have autologous, allogeneic, or xenogeneic origin. Moreover, they may be cellular or acellular. They are used to accelerate wound healing and recover normal skin functions with pain relief. Although there are a wide variety of commercially available skin substitutes, almost none of them considered as an ideal equivalents required for proper wound healing.

Adipose Tissue-Derived Stromal Cells for Wound Healing.

Skin as the outer layer covers the body. Wounds can affect this vital organ negatively and disrupt its functions. Wound healing as a biological process is initiated immediately after an injury. This process consists of three stages: inflammation, proliferation, remodeling. Generally, these three stages occur continuously and timely. However, some factors such as infection, obesity and diabetes mellitus can interfere with these stages and impede the normal healing process which results in chronic wounds. Financial burden on both patients and health care systems, negative biologic effect on the patient's general health status and reduction in quality of life are a number of issues which make chronic wounds as a considerable challenge. During recent years, along with advances in the biomedical sciences, various surgical and non-surgical therapeutic methods have been suggested. All of these suggested treatments have their own advantages and disadvantages. Recently, cell-based therapies and regenerative medicine represent promising approaches to wound healing. Accordingly, several types of mesenchymal stem cells have been used in both preclinical and clinical settings for the treatment of wounds. Adipose-derived stromal cells are a cost-effective source of mesenchymal stem cells in wound management which can be easily harvest from adipose tissues through the less invasive processes with high yield rates. In addition, their ability to secrete multiple cytokines and growth factors, and differentiation into skin cells make them an ideal cell type to use in wound treatment. This is a concise overview on the application of adipose-derived stromal cells in wound healing and their role in the treatment of chronic wounds.

Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.

In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity. These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers. It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.