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Over the past years, stem cell technology was heralded as a significant breakthrough of the century in scrutinizing the intricacies of human body biology and discovering different therapeutic approaches. Recently, adipose tissue, as a suitable source of harvesting mesenchymal stem cells, has attracted the attention of many researchers in the field of regenerative medicine. Adipose tissue-derived mesenchymal stem cells can self-renew and differentiate into different types of cells such as adipocytes, chondrocytes, and osteoblasts. Adipose tissue, especially brown type, is considered an attractive cell source for various therapeutic purposes, such as restoring damaged tissue or fighting against diseases such as obesity. The growth of importance of stem cell applications in regenerative medicine has highlighted the need to seek appropriate mesenchymal stem cells sources. Recently, in the light of many efforts in the field of regenerative medicine, mice have gained increasing interest as a suitable source of adipose tissue for the extraction of mesenchymal stem cells, which can be used in the preclinical investigations in order to aid in the treatment of many human diseases.

Different biomaterials have been used as biological dressing for wound regeneration. For many decades, human amniotic membrane graft (AM) has been widely applied for treating acute and chronic wounds. It has minimal toxicity and immunogenicity, supports mesenchymal cell in-growth, improves epidermal cell adherence and proliferation, and finally is inexpensive and readily available. Enrichment of tissue grafts with the stem cells is a new approach to improve their regenerative effects. This animal study aimed at investigating feasibility, safety, and efficacy of tissue-engineered dressings composed of AM and two different types of mesenchymal stem cells (MSCs) in the excisional wound model in rats. Human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs) were manufactured from the donated adipose and placenta tissues respectively. After cell characterization, MSCs were seeded on acellular AM (AAM) and cultivated for 5 days. Excisional wound model was developed in 24 male Wistar rats that were randomly classified into four groups including control, AAM, ADMSCs + AAM, and PLMSCs + AAM (n = 6 in each group). Tissue-engineered constructs were applied, and photographs were taken on days 0, 7, and 14 for observing the wound healing rates. In days 7 and 14 post-treatment, three rats from each group were euthanized, and wound biopsies were harvested, and histopathologic studies were conducted. The results of wound closure rate, re-epithelialization, angiogenesis, and collagen remodeling demonstrated that in comparison with the control groups, the MSC-seeded AAMs had superior regenerative effects in excisional wound animal model. Between MSCs group, the PLMSCs showed better healing effect. Our data suggested that seeding of MSCs on AAM can boosts its regenerative effects in wound treatment. We also found that PLMSCs had superior regenerative effects to ADMSc in the rat model of excisional wound.

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.

Severe acute respiratory syndrome-coronavirus 2, a novel betacoronavirus, has caused the global outbreak of a contagious infection named coronavirus disease-2019. Severely ill subjects have shown higher levels of pro-inflammatory cytokines. Cytokine storm is the term that can be used for a systemic inflammation leading to the production of inflammatory cytokines and activation of immune cells. In coronavirus disease-2019 infection, a cytokine storm contributes to the mortality rate of the disease and can lead to multiple-organ dysfunction syndrome through auto-destructive responses of systemic inflammation. Direct effects of the severe acute respiratory syndrome associated with infection as well as hyperinflammatory reactions are in association with disease complications. Besides acute respiratory distress syndrome, functional impairments of the cardiovascular system, central nervous system, kidneys, liver, and several others can be mentioned as the possible consequences. In addition to the current therapeutic approaches for coronavirus disease-2019, which are mostly supportive, stem cell-based therapies have shown the capacity for controlling the inflammation and attenuating the cytokine storm. Therefore, after a brief review of novel coronavirus characteristics, this review aims to explain the effects of coronavirus disease-2019 cytokine storm on different organs of the human body. The roles of stem cell-based therapies on attenuating cytokine release syndrome are also stated.

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.

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.

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.

Mesenchymal stem cells are one of the most attractive sources for stem cell research and therapy. Their safety and efficacy have been demonstrated in many clinical trials. Because of their low immunogenicity and immunomodulatory properties, allogenic MSCs have been transplanted in different clinical studies. MSCs could be in different adult- and fetal-derived tissues including pregnancy products. Placenta-derived mesenchymal stem cells (PLMSCs) that can be harvested without using any invasive procedures from a discarding tissue are one of the important types of mesenchymal stem cells for therapeutic applications. Stem cell manufacturing for therapeutic applications should be in compliance with the basic principles of good manufacturing practice (GMP). Herein, the current chapter is to describe GMP-compliant production of human PLMSCs, which are suitable for clinical applications.

Schwann cells as glial cells in the peripheral nervous system can participate in neurons protection and forming myelin. Additionally, they are important for nerve pulse conduction supporting along axons. On the other hand, it was demonstrated that they are promising cells for the treatment of demyelinating disorders and also central nervous system damages. Herein, for therapeutic application, Schwann cells should be manufactured based on good manufacturing practice standards to achieve safe and effective clinical products. In this respect, the current chapter tries to introduce a standard protocol for manufacturing of human GMP-compliant Schwann cells for clinical application.

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.

Schwann cells as glial cells in the peripheral nervous system can participate in neurons protection and forming myelin. Additionally, they are important for nerve pulse conduction supporting along axons. On the other hand, it was demonstrated that they are promising cells for the treatment of demyelinating disorders and also central nervous system damages. Herein, for therapeutic application, Schwann cells should be manufactured based on good manufacturing practice standards to achieve safe and effective clinical products. In this respect, the current chapter tries to introduce a standard protocol for manufacturing of human GMP-compliant Schwann cells for clinical application.

Cell therapy, as a field of biotherapeutic medicines, concerns with global public health promotion. The complexity of human cell- and tissue-based products (HCTPs) in their structure, content, mode of action, and delivery confronts health relevant professionals, regulatory authorities, and manufacturers with some challenges from product design to delivery [1].

Mesenchymal stem cells are one of the most attractive sources for stem cell research and therapy. Their safety and efficacy have been demonstrated in many clinical trials. Because of their low immunogenicity and immunomodulatory properties, allogenic MSCs have been transplanted in different clinical studies. MSCs could be in different adult- and fetal-derived tissues including pregnancy products. Placenta-derived mesenchymal stem cells (PLMSCs) that can be harvested without using any invasive procedures from a discarding tissue are one of the important types of mesenchymal stem cells for therapeutic applications. Stem cell manufacturing for therapeutic applications should be in compliance with the basic principles of good manufacturing practice (GMP). Herein, the current chapter is to describe GMP-compliant production of human PLMSCs, which are suitable for clinical applications.

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.

Background Among different kinds of cells involved in the wound healing process, fibroblasts play a pivotal role in the proliferation phase of this procedure wherein they induce the production of local growth factors and cytokines. Fetal fibroblasts with low immunogenic property and different wound healing process could be considered as a suitable alternative to neonatal foreskin cell based products in regenerative medicine and cell therapy. Cell therapy is an almost newly introduced method in the medical field and is also a challenging issue, which should assure the safety of the final product and the absence of viral or bacterial contamination with minimal immunogenic response. Therefore, based on current GMP (cGMP) principles, it is a matter of great importance to monitor raw materials’ quality and the conformity of all production procedures including cell culture, collection, and cryopreservation with validated standard operating procedures (SOPs). In the current study, we demonstrated the GMP-compatible and clinical-grade fetal fibroblast cells banking to be used for clinical applications.Methods All steps of isolation and culturing and cryopreservation of fetal fibroblast cells were performed under the sterile condition according to cGMP guidelines in the clean room. During the cell culture procedures, bacteriological investigation was performed in order to identify the probable contamination of the samples.Results Isolated fetal dermal fibroblasts were harvested and stored at early passages. The viability of fibroblasts was ≥ 98%, indicating successful establishment of fibroblast banking. Flow cytometry analysis has revealed the high purity of isolated and cultured fibroblastic population Karyotyping of fibroblasts at the 10th subculture shows a normal diploid male pattern.Conclusions The manufactured cells, according to the highest level of safety are considered as the most appropriate treatment option for cellular therapy. Based-on the current evidence, clinical-grade fetal fibroblasts throw new light on efficient and prompt healing of acute and chronic wounds of any etiology.

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.

Context: Multiple sclerosis (MS) is an autoimmune and inflammatory disease that affects the central nervous system (CNS). In MS, activated T-cells for self-antigens, such as myelin, attack erroneous targets in the CNS and result in axonal demyelination and neurological disability. Stem cell (SC) therapy has potential applications in treating neurological disorders. Evidence Acquisition: The reasoning for use of SCs from different sources, as a therapeutic option in MS, arose from the expectation that they have the capacity to remyelinate and differentiate into oligodendrocyte precursor cells. Many SC types are under testing for treating MS and, the most common, are neural SC (NSC), embryonic SC (ESC), mesenchymal SC (MSC) and hematopoietic SC (HSC). Results: The NSCs, namely adult NSCs, bone marrow-derived-NSCs and neural progenitor cells, are capable of differentiation into oligodendrocytes and induce remyelination. The MSCs influence on the rate of repair of all endogenous progenitors. The autologous HSC transplantation is an option in cases that do not respond to standard therapy and also meliorate the symptoms and limit progression of disease. The ESCs have shown neuroprotection in cases of MS, through a yet unclear immunosuppression mechanism. Conclusions: Recently, cell transplantation has introduced a novel approach for treatment of neurological disorders, such as MS. Therefore, focusing on safety issues, while bridging from the basic SC sciences to the clinical transplantation trials, has a crucial role in cellular therapy programs. This review will discuss in detail the experimental and clinical use of these SC populations and their probably mechanisms in the treatment of multiple sclerosis.

Regenerative medicine as a novel approach uses biological methods and products to regenerate, repair, replace, and enhance the lost function of an organ or tissue. Stem cells have a crucial role in regenerative medicine. Therefore, several sources of stem cells have been used for cell therapy, tissue engineering and regenerative medicine. Recently, perinatal stem cells as a promising cell source have been suggested for regenerative medicine. Their great advantages such as convenient accessibility, low immunogenicity, high proliferation capacity, and minimal ethical limitations have introduced them as a novel source for regenerative medicine. However, good manufacturing practice (GMP) is needed to provide these cells with defined quality, safety, and efficacy for clinical application. Like to other types of stem cells, perinatal stem cells manufacturing in accordance with GMP regulations and standards could provide a valuable source of stem cells for cell therapy and regenerative medicine.

Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.