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.

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.

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.

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.

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.

Cell Therapy Targets for Autism Spectrum Disorders: Hopes, Challenges and Future Directions.

Autism spectrum disorders as a group of pediatric neurodevelopmental diseases is a crucial part of the worldwide disabilities which have influence in communication skills, social interactions, and ability to understand the concepts. The precise pathophysiology of autism spectrum disorders due to the abundance of involved mechanisms is unknown. Some of these involved mechanisms are related to genetic factors, chronic neuro inflammation, mitochondrial dysfunction, oxidative stress, immune dysregulation, hormonal imbalance, and environmental factors. Current main treatments for autisms are behavioral, nutritional and medical therapies, however there is not definitive treatment approach. Therein, more novel therapies are still required to improve the symptoms. Several preclinical and clinical evidence were shown that stem cell therapy is a potential treatment option for autism spectrum disorders individuals. Considering the significant factors which can affect the outcome of stem cell therapeutic effects including stem cell types, route and dosage of administration, and mechanism of activity along with selecting best animal models can be very important in performing clinical trials.

Regenerative Medicine Perspectives in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common gynecologic endocrine disorder in women between the ages of 15 and 40, with uncertain etiology. It is mostly presented with hyperandrogenism and insulin resistance along with a variety of comorbidities that significantly reduce a patient's quality of life. Many disturbed metabolic pathways are correlated with PCOS. Moreover, it is evident that there is a strong genetic factor for PCOS. Indeed, several altered gene expressions have been found in PCOS subjects, but the exact genetic origins are still unclear. The major treatment options such as pharmacological treatments are to improve the symptoms. In addition, surgical procedures (Bariatric surgery and assisted reproductive technologies) can be used to treat some of the patient's complications and reduce their severity. Generally, using pharmacological agents for a long period of time can increase the risk of adverse effects. Moreover, surgical options may have high-risk consequences. Herein, there is an undeniable need for a different multidisciplinary approach to PCOS. Regenerative medicine with the help of stem cells can develop a worthy alternative approach for the treatment of PCOS. Furthermore, animal models can provide valuable knowledge of genetic alterations and metabolic pathway disturbances in PCOS. They can also be used for testing novel treatments in pre-clinical stages. Therein, the current knowledge of PCOS and investigation about the potential role of regenerative medicine in developing new and more efficient treatments for PCOS are summarized here.

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.

Stem cell-based models and therapies: a key approach into schizophrenia treatment.

Psychiatric disorders such as schizophrenia can generate distress and disability along with heavy costs on individuals and health care systems. Different genetic and environmental factors play a pivotal role in the appearance of the mentioned disorders. Since the conventional treatment options for psychiatric disorders are suboptimal, investigators are trying to find novel strategies. Herein, stem cell therapies have been recommended as novel choices. In this context, the preclinical examination of stem cell-based therapies specifically using appropriate models can facilitate passing strong filters and serious examination to ensure proper quality and safety of them as a novel treatment approach. Animal models cannot be adequately helpful to follow pathophysiological features. Nowadays, stem cell-based models, particularly induced pluripotent stem cells reflected as suitable alternative models in this field. Accordingly, the importance of stem cell-based models, especially to experiment with the regenerative medicine outcomes for schizophrenia as one of the severe typing of psychiatric disorders, is addressed here.

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.

The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges.

Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. The emergence of recombinant DNA technology which provides the possibility of fetal genetic screening and genetic counseling is a good case in point. Therefore, gene therapy advances are being applied to correct inherited genetic disorders such as hemophilia, cystic fibrosis, and familial hypercholesterolemia as well as acquired diseases like cancer, AIDS, Alzheimer's disease, Parkinson's disease, and infectious diseases like HIV. As a result, gene therapy approaches have the ability to help the vast majority of newborns with different diseases. Since these ongoing treatments and clinical trials are being developed, many more barriers and challenges have been created. In order to continue this positive growth, these challenges need to be recognized and addressed. Accordingly, safety, efficiency and also risks and benefits of gene therapy trials for each disease should be considered. As a result, sustained manufacturing of the therapeutic gene product without any harmful side effects is the least requirement for gene therapy. Herein, different aspects of gene therapy, an overview of the progress, and also the prospects for the future have been discussed for the successful practice of gene therapy.

Cell-based approaches towards treating age-related macular degeneration.

Age-related macular degeneration as one of the most common causes of worldwide vision loss needs a proper approach for treatment. Therein, cell therapy and regenerative medicine can hold a great promise to be an effective approach. Accordingly, some preclinical and clinical studies were conducted to search around the therapeutic influence of stem cells in Age-related macular degeneration models and subjects. Hereupon, the purpose of the current review is to discuss the mechanisms of age-related macular degeneration, appropriate animal models along with suitable dosage and route of stem cell administration for its treatment.

Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19.

Acute respiratory infections as one of the most common problems of healthcare systems also can be considered as an important reason for worldwide morbidity and mortality from infectious diseases. Coronaviruses are a group of well-known respiratory viruses that can cause acute respiratory infections. At the current state, the 2019 novel coronavirus is cited as the most worldwide problematic agent for the respiratory system. According to investigations, people with old age and underlying diseases are at higher risk of 2019 novel coronavirus infection. Indeed, they may show a severe form of the disease (with severe acute respiratory infections). Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by the 2019 novel coronavirus. Herein, due to the amazing effects of mesenchymal stem cells in the treatment of various diseases, this review focuses on the auxiliary role of mesenchymal stem cells to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus.

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.

Development and validation of Alzheimer's Disease Animal Model for the Purpose of Regenerative Medicine.

One of the most common age-related neurodegenerative disorders is Alzheimer's disease which globally threatening the health of elderly people. Although there are several pharmacological and non- pharmacological treatments for Alzheimer's disease, they can just decrease the symptoms in these diseases. In this context, cell therapy and regenerative medicine approach as the novel therapeutic strategies for neurodegenerative diseases would be important. Based on scientific research principles, using any novel therapeutic approaches before the run in clinical trials need to take preclinical (animal study) stapes. Accordingly, an animal study can improve our understanding of biological mechanisms of diseases and as an important step should adhering to ethical guidelines and standards. On the other hand, to gain suitable outcomes, it is important to check the appropriate validation of animal models. In this regard, the present review would discuss about the development and validation of appropriate AD animal models in the field of regenerative medicine.

Stem Cell and Obesity: Current State and Future Perspective.

Obesity as a worldwide growing challenge is determined by abnormal fat deposition, which may damage general health. Weight loss and control of related risk factors like type2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, and metabolic syndrome is an important concern in obesity management. Different therapeutic approaches such as lifestyle change, medications, and surgery are introduced for obesity treatment. Despite of gaining partially desirable results, the problem is remained unsolved. Therefore, finding a new approach that can overcome previous limitations is very attractive for both researchers and clinicians. Cell-based therapy using adipose-derived stromal cells seems to be a promising strategy to control obesity and related syndromes. To attain this aim, understanding of different type of adipose tissues, main signaling pathways, and different factors involved in development of adipocyte is essential. Recently, several cell-based methods like stem cell administration, brown adipose tissue transplantation, cell lysates and exosomes have been examined on obese mouse models to manage obesity and related disorders. Successful outcome of such preclinical studies can encourage the cell-based clinical trials in the near future.

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.

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.