Zebrafish Modeling of Autism Spectrum Disorders, Current Status and Future Prospective.

Autism spectrum disorder (ASD) refers to a complicated range of childhood neurodevelopmental disorders which can occur via genetic or non-genetic factors. Clinically, ASD is associated with problems in relationships, social interactions, and behaviors that pose many challenges for children with ASD and their families. Due to the complexity, heterogeneity, and association of symptoms with some neuropsychiatric disorders such as ADHD, anxiety, and sleep disorders, clinical trials have not yielded reliable results and there still remain challenges in drug discovery and development pipeline for ASD patients. One of the main steps in promoting lead compounds to the suitable drug for commercialization is preclinical animal testing, in which the efficacy and toxicity of candidate drugs are examined in vivo. In recent years, zebrafish have been able to attract the attention of many researchers in the field of neurological disorders such as ASD due to their outstanding features. The presence of orthologous genes for ASD modeling, the anatomical similarities of parts of the brain, and similar neurotransmitter systems between zebrafish and humans are some of the main reasons why scientists draw attention to zebrafish as a prominent animal model in preclinical studies to discover highly effective treatment approaches for the ASD through genetic and non-genetic modeling methods.

Recent Advances of COVID-19 Modeling Based on Regenerative Medicine.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused a pandemic since December 2019 that originated in Wuhan, China. Soon after that, the world health organization declared Coronavirus disease-2019 a global health concern. SARS-CoV-2 is responsible for a lethal respiratory infection as well as the involvement of other organs due to its large tropism spectrum such as neurologic, cardiovascular, endocrine, gastrointestinal, and renal systems. Since the behavior of the virus is not fully understood, a new manifestation of the infection is revealed every day. In order to be able to design more efficient drugs and vaccines to treat the infection, finding out the exact mechanism of pathogenicity would be necessary. Although there have been some big steps toward understanding the relevant process, there are still some deficiencies in this field. Accordingly, regenerative medicine (RM), can offer promising opportunities in discovering the exact mechanisms and specific treatments. For instance, since it is not always possible to catch the pathophysiology mechanisms in human beings, several modeling methods have been introduced in this field that can be studied in three main groups: stem cell-based models, organoids, and animal models. Regarding stem cell-based models, induced pluripotent stem cells are the major study subjects, which are generated by reprogramming the somatic stem cells and then directing them into different adult cell populations to study their behavior toward the infection. In organoid models, different cell lines can be guided to produce a 3D structure including liver, heart, and brain-like platforms. Among animal models, mice are the most common species in this field. However, in order for mice models to be permissive to the virus, angiotensin-converting enzyme 2 receptors, the main receptor involved in the pathogenicity of the virus, should be introduced to the host cells through different methods. Here, the current known mechanism of SARS-CoV-2 infection, different suggested models, the specific response toward different manipulation as well as challenges and shortcomings in each case have been reviewed. Finally, we have tried to provide a quick summary of the present available RM-based models for SARS-CoV-2 infection, as an essential part of developing drugs, for future therapeutic goals.

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.

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.

Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives.

Systemic sclerosis is a rare chronic autoimmune disease with extensive microvascular injury, damage of endothelial cells, activation of immune responses, and progression of tissue fibrosis in the skin and various internal organs. According to epidemiological data, women's populations are more susceptible to systemic sclerosis than men. Until now, various therapeutic options are employed to manage the symptoms of the disease. Since stem cell-based treatments have developed as a novel approach to rescue from several autoimmune diseases, it seems that stem cells, especially mesenchymal stem cells as a powerful regenerative tool can also be advantageous for systemic sclerosis treatment via their remarkable properties including immunomodulatory and anti-fibrotic effects. Accordingly, we discuss the contemporary status and future perspectives of mesenchymal stem cell transplantation for systemic sclerosis.

Metabolomics and Cell Therapy in Diabetes Mellitus.

Diabetes with a broad spectrum of complications has become a global epidemic metabolic disorder. Till now, several pharmaceutical and non-pharmaceutical therapeutic approaches were applied for its treatment. Cell-based therapies have become promising methods for diabetes treatment. Better understanding of diabetes pathogenesis and identification of its specific biomarkers along with evaluation of different treatments efficacy, can be possible by clarification of specific metabolic modifications during the diabetes progression. Subsequently, metabolomics technology can support this goal as an effective tool. The present review tried to show how metabolomics quantifications can be useful for diabetic monitoring before and after cell therapy. Cell therapy is an alternative approach to achieve diabetes treatments goals including insulin resistance amelioration, insulin independence reparation, and control of glycemia. OMICs approaches provide a comprehensive insight into the molecular mechanisms of cells features and functional mechanism of their genomics, transcriptomics, proteomics, and metabolomics profile which can be useful for their therapeutic application. As a modern technology for the detection and analysis of metabolites in biological samples, metabolomica can identify many of the metabolic and molecular pathways associated with diabetes and its following complications.