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The OBJECTIVE was to study the process of wound healing after surgical interventions in patients with urgent surgical diseases in combination with a new coronavirus infection. METHODS AND MATERIALS. We observed for 80 patients with urgent abdominal diseases. Group I – 48 patients with various urgent diseases of the abdominal organs, group II – 32 patients with similar diseases occurring against the background of coronavirus infection. Stages of postoperative examination: 2, 4 and 7 days after surgery. The nature and rate of wound regeneration was assessed by cytological examination of wound exudate. In the tissues along the suture line, trophic indicators and microcirculation were recorded. RESULTS. The number of neutrophilic leukocytes in the wound exudate in group II exceeded the values of group I by 38.7–116.8 % with a slowed down dynamics of recovery. In the II group of patients, the number of tissue polyblasts was reduced at all stages of observation in comparison with the control group by 34.2–41.9 %. The number of lymphoid polyblasts in the main group was increased in comparison with the control group on days 2, 4, 7 of observation by 33.1 %, 63.2 %, 354.9 %, respectively. The indices of microcirculation in the tissues of the laparotomic wound in the group II of patients changed to a greater extent. The redox potential and oxygen diffusion coefficient in the group II were lower than the control figures by 9.8 – 37.2 % and 35.3 – 38.1 %, respectively. The number of complications according to the Clavien – Dindo classification in the group II of patients compared to the group I was more than 6 times higher. CONCLUSION. In patients with urgent diseases of the abdominal organs with concomitant coronavirus infection, the process of incomplete reparative tissue regeneration of the wound area slows down, which increases the risk of complications. The main factors that reduce the rate of tissue healing are disorders of microcirculation and bioenergetics. © 2022 Authors. All rights reserved.
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Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and repair, secreting vesicles to the extracellular environment. Isolated exosomes were shown to affect angiogenesis, immunomodulation and tissue regeneration. Numerous efforts have been dedicated to describe the mechanism of action of these extracellular vesicles (EVs) and guarantee their safety, since the final aim is their therapeutic application in the clinic. The major advantage of applying MSC-derived EVs is their low or inexistent immunogenicity, prompting their use as drug delivery or therapeutic agents, as well as wound healing, different cancer types, and inflammatory processes in the neurological and cardiovascular systems. MSC-derived EVs display no vascular obstruction effects or apparent adverse effects. Their nano-size ensures their passage through the blood-brain barrier, demonstrating no cytotoxic or immunogenic effects. Several in vitro tests have been conducted with EVs obtained from different sources to understand their biology, molecular content, signaling pathways, and mechanisms of action. Application of EVs to human therapies has recently become a reality, with clinical trials being conducted to treat Alzheimer's disease, retina degeneration, and COVID-19 patients. Herein, we describe and compare the different extracellular vesicles isolation methods and therapeutic applications regarding the tissue repair and regeneration process, presenting the latest clinical trial reports.
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Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of 'biomaterials', and a typical new insight is the concept of tissue induction biomaterials. The term 'regenerative biomaterials' and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field-regenerative biomaterials.
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Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 with severe respiratory failure and organ damage that later appeared as a pandemic disease. Worldwide, people's mental and physical health and socioeconomic have been affected. Currently, with no promising treatment for COVID-19, the existing anti-viral drugs and vaccines are the only hope to boost the host immune system to reduce morbidity and mortality rate. Unfortunately, several reports show that people who are partially or fully vaccinated are still susceptible to COVID-19 infection. Evidence suggests that COVID-19 immunopathology may include dysregulation of macrophages and monocytes, reduced type 1 interferons (IFN-1), and enhanced cytokine storm that results in hypersecretion of proinflammatory cytokines, capillary leak syndrome, intravascular coagulation, and acute respiratory distress syndrome (ARDS) ultimately leading to the worsening of patient's condition and death in most cases. The recent use of cell-based therapies such as mesenchymal stem cells (MSCs) for critically ill COVID-19 patients has been authorized by the Food and Drug Administration (FDA) to alleviate cytokine release syndrome. It protects the alveolar epithelial cells by promoting immunomodulatory action and secreting therapeutic exosomes to improve lung function and attenuate respiratory failure. As a result, multiple clinical trials have been registered using MSCs that aim to use various cell sources, and dosages to promote safety and efficacy against COVID-19 infection. In this review, the possibility of using MSCs in COVID-19 treatment and its associated challenges in their use have been briefly discussed.
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Viruses lacking the capacity to infect mammals exhibit minimal toxicity, good biocompatibility, and well-defined structures. As self-organized biomolecular assemblies, they can be produced from standard biological techniques on a large scale at a low cost. Genetic, chemical, self-assembly, and mineralization techniques have been applied to allow them to display functional peptides or proteins, encapsulate therapeutic drugs and genes, assemble with other materials, and be conjugated with bioactive molecules, enabling them to bear different biochemical properties. So far, a variety of viruses (infecting bacteria, plants, or animals), as well as their particle variants, have been used as biomaterials to advance human disease prevention, diagnosis, and treatment. Specifically, the virus-based biomaterials can serve as multifunctional nanocarriers for targeted therapy, antimicrobial agents for infectious disease treatment, hierarchically structured scaffolds for guiding cellular differentiation and promoting tissue regeneration, versatile platforms for ultrasensitive disease detection, tissue-targeting probes for precision bioimaging, and effective vaccines and immunotherapeutic agents for tackling challenging diseases. This review provides an in-depth discussion of these exciting applications. It also gives an overview of the viruses from materials science perspectives and attempts to correlate the structures, properties, processing, and performance of virus-based biomaterials. It describes the use of virus-based biomaterials for preventing and treating COVID-19 and discusses the challenges and future directions of virus-based biomaterials research. It summarizes the progressive clinical trials of using viruses in humans. With the impressive progress made in the exciting field of virus-based biomaterials, it is clear that viruses are playing key roles in advancing important areas in biomedicine such as early detection and prevention, drug delivery, infectious disease treatment, cancer therapy, nanomedicine, and regenerative medicine. © 2023 Elsevier B.V.
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BACKGROUND: Corona Virus Disease 2019 (COVID-19) is a highly contagious, rapidly variable, and dangerous infectious disease. However, no specific and effective treatment for COVID-19 is available until now. The safety and efficacy of mesenchymal stem cells and their exosomes have been well verified in numerous clinical trials. Their immunomodulatory and tissue regeneration capabilities may support them as a prospective therapy for COVID-19 application in the clinic. OBJECTIVE: To focus on the development, pathogenesis and the current treatment status of COVID-19, efficacy and possible immunomodulatory mechanisms of mesenchymal stem cells and their exosomes for COVID-19 so as to provide new insights into the clinical treatment for the disease in the future. METHODS: Articles were searched on PubMed and CNKI with the key words of "SARS-CoV-2, COVID-19, cytokine storm, acute respiratory distress syndrome, mesenchymal stem cells, exosomes, immune regulation, tissue repair” in Chinese and English. Finally, 64 articles were collected for this review. RESULTS AND CONCLUSION: Acute respiratory distress syndrome and acute lung injury caused by cytokine storm are the primary precipitating factors of death in individuals with COVID-19. Mesenchymal stem cells and their exosomes can effectively treat the symptoms of acute respiratory distress syndrome and repair the damaged lung tissue in COVID-19 patients by reducing the cytokine storm and promoting the regeneration of alveolar epithelial cells through the interaction with immune cells and their paracrine effects. All of these investigations confirmed that mesenchymal stem cells and their exosomes can fight the COVID-19 infection, and this might be a promising, safe and effective strategy. However, more preclinical studies and randomized, controlled clinical trials are needed to conduct the biodistribution, metabolic fate, and the potential treatment risks of mesenchymal stem cells and their derived exosomes in vivo to fully exploit their clinical efficacy. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.
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The global anxiety and economic crisis causes the deadly pandemic coronavirus disease of 2019 (COVID 19) affect millions of people right now. Subsequently, this life threatened viral disease is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, morbidity and mortality of infected patients are due to cytokines storm syndrome associated with lung injury and multiorgan failure caused by COVID 19. Thereafter, several methodological advances have been approved by WHO and US-FDA for the detection, diagnosis and control of this wide spreadable communicable disease but still facing multi-challenges to control. Herein, we majorly emphasize the current trends and future perspectives of nano-medicinal based approaches for the delivery of anti-COVID 19 therapeutic moieties. Interestingly, Nanoparticles (NPs) loaded with drug molecules or vaccines resemble morphological features of SARS-CoV-2 in their size (60–140 nm) and shape (circular or spherical) that particularly mimics the virus facilitating strong interaction between them. Indeed, the delivery of anti-COVID 19 cargos via a nanoparticle such as Lipidic nanoparticles, Polymeric nanoparticles, Metallic nanoparticles, and Multi-functionalized nanoparticles to overcome the drawbacks of conventional approaches, specifying the site-specific targeting with reduced drug loading and toxicities, exhibit their immense potential. Additionally, nano-technological based drug delivery with their peculiar characteristics of having low immunogenicity, tunable drug release, multidrug delivery, higher selectivity and specificity, higher efficacy and tolerability switch on the novel pathway for the prevention and treatment of COVID 19. © 2022 The Author(s)
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This study was conducted to test the hypothesis that platelet-rich plasma (PRP) therapy in chronic respiratory disease patients will cause lung regeneration, thereby slowing the progression of the disease. We performed a search to obtain pertinent articles on the following electronic databases: Google Scholar, PubMed, NCBI, Medscape, and clinicaltrials.gov. Keywords used during in search included "Platelet Rich Plasma" AND "Chronic Respiratory Disease" AND/OR "Chronic Obstructive Pulmonary Disease". A total of 15 articles were chosen for this paper, published from 2011 to 2021, and included case series, lab studies, animal studies, cohort studies, and clinical trials. All statistical data were considered significant if the p-value was less than 5%, or 0.05. Our findings confirmed that PRP therapy successfully caused anti-inflammatory effects and acceleration of tissue regeneration, resulting in improved lung function. This, in turn, slowed the progression of the disease and led to an improved quality of life. Not all chronic respiratory disease patients present in the same manner, but the connecting link is the damaged tissue of the lungs, causing issues with the functionality of the lungs. By adjunctively treating patients with PRP, the high concentration of platelets and their secreted growth factors can help induce an acceleration of healing and regeneration of pulmonary tissue. This, in turn, can slow the progression of the disease, which could lower the overall mortality rate in chronic respiratory disease patients. More studies should be conducted on this topic, specifically large, double-blinded, randomized human trials with controls, to further assess the efficacy and beneficial effects of PRP treatment on the lungs.
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Purpose/Objectives: The increase in life expectancy in recent years is closely related to scientific advances in health area. Thus, longevity led to a greater emergence of chronic diseases, such as diabetes mellitus (DM). In this scenario, chronic wounds represent a serious public health problem. It is estimated that 85% of lower extremity amputations in individuals with DM are related to the presence of foot ulcers. The perception of changes in the skin, such as deformities, superficial traumas and cracks, is impaired in diabetics due to loss of sensitivity, predisposing the appearance of wounds. Ulcers and other injuries can be prevented through simple measures, such as regular skin inspection, specialized care and the use of adequate footwear;as the greater understanding of self-care, the greater the benefits of treatment. In this sense, Primary Care is an effective mean of assisting such individuals, as health education actions can be carried out for this population, their families and caregivers, with a view of promoting health. In addition, the health education process must take place in parallel with medication and dressings, which are essential, especially the latter, given the specificity of the product and the level of tissue regeneration. The primary objective of this study is to present the educational activities developed by the Extension Project Physiotherapy in the Community of the State University of Paraíba in partnership with the research project Tissue Engineering in Epithelial Repair: Biodegradable Scaffold for Tissue Regeneration, which is developing chitosan/Jatropha mollissima scaffolds, in the Laboratory of Evaluation and Development of Biomaterials from the Northeast of the Federal University of Campina Grande. Methodology: The participants consisted of users of Basic Health Units (BHU) in the city of Campina Grande/Paraiba/Brazil. The educational material on Diabetes and Diabetic Foot Wound Care was produced from documents such as articles, guidelines and booklets. The CANVA application was used to create the images and infographics, to facilitate the understanding of the participants, and it was sent along with an explanatory audio. The disclosure took place on the public profile on Instagram @fisionacomunidadeuepb and also through the WhatsApp application for the diabetic elderly who participate in the project, in addition to face-to-face meetings at BHU, to clarify doubts at previously scheduled times and with a limited number of people due to the covid 19 pandemic. Results: The results included a greater understanding of the process of illness and wound development, as well as awareness of the importance of adherence to treatment and care in the use of dressings, especially. According to the records, the participation in the means used was intense, which suggests that these people will also be multipliers in the health education process. Conclusion/Significance: It is concluded that health education strategies, even at the time of a pandemic, are useful in the process of correct information dissemination, helping the most vulnerable population to understand their disease and, at the same time, help them in self care and responsibility, thus facilitating the intervention used by the health and engineering team.
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From December 2019, COVID-19 pandemic has hit the human civilization in an unprecedented way. It has taken more than five million lives in just a span of two years. Two major mechanisms via which COVID-19 affects us are either via direct respiratory disorder and lung failure or otherwise via delayed flare of immune systems more prevalently known as the cytokine storm. Mesenchymal stem cells (MSCs) can be a potential therapeutic agent against mortality and morbidity of COVID-19 via direct differentiation into pulmonary epithelial cells as well as via antiinflammatory paracrine activities. MSCs are also can be useful to replicate COVID-19 infection in an in vitro organ model. In current study, we are systematically reviewing and finding out the potential applications of MSCs which could help mankind to combat COVID-19. © 2022 Elsevier Inc. All rights reserved.
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The COVID-19 outbreak emerged as a major health problem affecting the entire world. The need for specific drugs to treat COVID-19 infection has changed research interests to focus on stem cells to treat COVID-19, especially the severe cases. COVID-19 infection can lead to a proinflammatory cytokine storm, leading to inflammatory syndrome, tissue damage, tissue resident stem cell loss, and reduced tissue regeneration and repair. Stem cell therapy has already been used in treating lung diseases with promising results. Researchers have used human pluripotent stem cell-derived organoids to study how COVID-19 affects various tissues. Among the different types of stem cells, mesenchymal stem cells (MSCs) have gained more attention as a cell therapy for treating the COVID-19 related cytokine storm and organ damage, due to their immense capacity to regenerate and their immunomodulatory and cytoprotective properties. Numerous clinical trials have been initiated with MSCs for treating severely ill COVID-19 patients. This chapter gives an overview of the possibilities of various stem cell populations in the management of COVID-19 related complications. © 2022 Elsevier Inc. All rights reserved.
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Context: Oral manifestations that arose from COVID-19 infection often causes morbidity and systemic drug administration is less effective. Roselle flower (Hibiscus sabdariffa) is one of the plants that is often used in infusion as it gives health benefits. Hence, H. sabdariffa may benefit from adjuvant therapy to treat oral manifestation due to COVID-19. Aims: To investigate the potential of H. sabdariffa anthocyanins, tartaric acid, and ascorbic acid chemical compounds as antiviral, anti-inflammatory, antioxidant, and increasing tissue regeneration in oral manifestation due to COVID-19 infection in silico. Methods: Chemical compounds consisted of anthocyanins, (+)-tartaric acid, and ascorbic acid beside target proteins consisted of ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR and MDA-ovalbumin were obtained from the database, ligand samples were selected through absorption, distribution, metabolism, excretion and toxicology analysis, then molecular docking simulations, identification of protein-ligand interactions, and 3D visualization were performed. Results: Anthocyanins, tartaric acid, and ascorbic acid are the active compounds in H. sabdariffa, which act as antioxidants. The activity of anthocyanin compounds is higher than other compounds through value binding affinity, which is more negative and binds to specific domains of target proteins by forming weak binding interactions that play a role in biological responses. Anthocyanins have the most negative binding energy compared to tartaric-acid and ascorbic acid. Conclusions: Anthocyanins act as antioxidants;this mechanism increases heat shock protein-70 (HSP70), which may play an important role in increasing wound regeneration of oral manifestation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as documented in silico.
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a highly contagious microorganism, and despite substantial investigation, no progress has been achieved in treating post-COVID complications. However, the virus has made various mutations and has spread around the world. Researchers have tried different treatments to reduce the side effects of the COVID-19 symptoms. One of the most common and effective treatments now used is steroid therapy to reduce the complications of this disease. Long-term steroid therapy for chronic inflammation following COVID-19 is harmful and increases the risk of secondary infection, and effective treatment remains challenging owing to fibrosis and severe inflammation and infection. Sometimes our immune system can severely damage ourselves in disease. In the past, many researchers have conducted various studies on the immunomodulatory properties of stem cells. This property of stem cells led them to modulate the immune system of autoimmune diseases like diabetes, multiple sclerosis, and Parkinson's. Because of their immunomodulatory properties, stem cell-based therapy employing mesenchymal or hematopoietic stem cells may be a viable alternative treatment option in some patients. By priming the immune system and providing cytokines, chemokines, and growth factors, stem cells can be employed to build a long-term regenerative and protective response. This review addresses the latest trends and rapid progress in stem cell treatment for Acute Respiratory Distress Syndrome (ARDS) following COVID-19.
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One option to improve tissue regeneration is the use of growth factors. As a promising alternative to recombinant protein therapy, gene therapy allows local and sustained release of growth factors. This moderate and constant release is more suitable for regenerative processes compared to administration of high protein doses. Exogenous growth factors are produced by cells in situ;such highly bioactive amounts of growth factors are produced directly at the defect site, thereby highly limiting adverse off-target effects. Targeted research areas include (combinatorial) gene therapy approaches for bone/musculoskeletal tissue regeneration in vivo and ex vivo. Amongst them, new techniques such as viral and non-viral gene delivery systems, next-generation therapeutical DNA vectors for example with decreased immunogenicity, enhanced bioactivity of growth factor and enhanced gene expression. Beside DNA based gene therapy also mRNA based technologies are increasingly used and becoming popular by Covid vaccination successes. Increasing records of clinical success in the last years have constantly improved awareness of gene therapy, strengthening the enthusiasm of the community for novel and effective treatment methods providing the needed momentum for further developments.
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Immunotherapy has reached clinical success in the last decade, with the emergence of new and effective treatments such as checkpoint blockade therapy and CAR T-cell therapy that have drastically improved patient outcomes. Still, these therapies can be improved to limit off-target effects, mitigate systemic toxicities, and increase overall efficacies. Nanoscale engineering offers strategies that enable researchers to attain these goals through the manipulation of immune cell functions, such as enhancing immunity against cancers and pathogens, controlling the site of immune response, and promoting tolerance via the delivery of small molecule drugs or biologics. By tuning the properties of the nanomaterials, such as size, shape, charge, and surface chemistry, different types of immune cells can be targeted and engineered, such as dendritic cells for immunization, or T cells for promoting adaptive immunity. Researchers have come to better understand the critical role the immune system plays in the progression of pathologies besides cancer, and developing nanoengineering approaches that seek to harness the potential of immune cell activities can lead to favorable outcomes for the treatment of injuries and diseases.
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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common clinical problem, leading to significant morbidity and mortality, and no effective pharmacotherapy exists. The problem of ARDS causing mortality became more apparent during the COVID-19 pandemic. Biotherapeutic products containing multipotent mesenchymal stromal cell (MMSC) secretome may provide a new therapeutic paradigm for human healthcare due to their immunomodulating and regenerative abilities. The content and regenerative capacity of the secretome depends on cell origin and type of cultivation (two- or three-dimensional (2D/3D)). In this study, we investigated the proteomic profile of the secretome from 2D- and 3D-cultured placental MMSC and lung fibroblasts (LFBs) and the effect of inhalation of freeze-dried secretome on survival, lung inflammation, lung tissue regeneration, fibrin deposition in a lethal ALI model in mice. We found that three inhaled administrations of freeze-dried secretome from 2D- and 3D-cultured placental MMSC and LFB protected mice from death, restored the histological structure of damaged lungs, and decreased fibrin deposition. At the same time, 3D MMSC secretome exhibited a more pronounced trend in lung recovery than 2D MMSC and LFB-derived secretome in some measures. Taking together, these studies show that inhalation of cell secretome may also be considered as a potential therapy for the management of ARDS in patients suffering from severe pneumonia, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, their effectiveness requires further investigation.
Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Pneumonia , Respiratory Distress Syndrome , Acute Lung Injury/therapy , Animals , COVID-19/therapy , Cell Culture Techniques , Female , Fibrin , Humans , Mesenchymal Stem Cell Transplantation/methods , Mice , Pandemics , Placenta , Pregnancy , Proteomics , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , SecretomeABSTRACT
Inflammation is a component of any tissue regeneration. Injury and tissue damage - including exogenous viral and bacterial infections - induce an early pro-inflammatory phase, which is further propagated by activation of both resident innate immune cells and cells recruited from peripheral blood and bone marrow. This pro-inflammatory stage is essential for clearance of cellular debris and to induce the regenerative process. However, to achieve successful tissue regeneration, it is essential to allow timely resolution of inflammation by initiation of an antiinflammatory phase of tissue regeneration. This phase can then be followed by new tissue formation, referred to as ?modeling? in the example of fracture healing. The rapidly formed new tissue is adapted to the physical needs in the final phase of regeneration, called ?remodeling? in case of fracture healing. If timely resolution of inflammation is missing, persistent inflammation prevents entry into the phase of new tissue formation and thus successful regeneration. Either scar healing occurs as a "stopgap"solution or tissue destruction is initiated. The deteriorating regenerative capacity of many tissues with age, including bone, muscle and tendon, occurs as a consequence of subclinical chronic inflammation of tissues that propagates aging (?inflammaging?). Inflammation in the micromillieu involves not only tissue-typical cells and their adult progenitors, but also the cells of the tissue?s resident innate immune system, above all macrophages. These are also subject to age-associated changes such as cellular aging and increased susceptibility to pro-inflammatory overreactions. Chronic inflammation ultimately leads to cellular senescence, which is accompanied by a senescence-associated secretory phenotype (SASP) with high production of interleukins 1, 6, 8, and other cytokines. As long as such cells do not enter regulated cell death, they maintain chronic inflammation, setting the stage for insufficient tissue regeneration. Inflammation can be self-sustaining in certain pathology and, in the worst case, can progress to a state of hyperinflammation that abolishes any regeneration, destroys tissue, and leads to tissue/organ failure. The best known example may be the highly active autoimmune hyperinflammation like in unmanaged rheumatoid arthritis. Infection with COVID-19 can cause a deleterious outcome of the disease with the same mechanism of hyperinflammation of the innate immune system. Here, hyperinflammation may exaggerate relatively independent of viral replication. COVID-19 directly stimulates NFkB-dependent pro-inflammatory secretion and initiates an IL6-dependent vicious circle, which is then amplified via innate immune system cells. COVID-19 also directly stimulates the so-called inflammasome of the cell. The virus also causes cellular senescence in this pro-inflammatory environment. Depending on the preload of senescent cells amenable to overstimulation for cytokine production, the greater the risk of a cytokine storm with a deleterious outcome. People of advanced age and those with chronic diseases accompanied by pro-inflammatory conditions such as severe obesity, diabetes, and arthritis consequently represent the high-risk populations for COVID-19 infection with a severe outcome. Of note, our target population for the treatment of osteoporosis and osteoarthritis meets this profile. In addition to antiviral therapeutic measures, it is equally important to address the mechanisms of hyperinflammation that result from, among other causes, the large preload and the additional senescent cells caused by COVID-19. We obviously have parallels that lie in the pathogenesis of tissue degeneration. It has been shown in animal models that osteoporosis responds to treatment with senolytics, and a clinical trial is underway. Severe COVID-19 infection was also significantly ameliorated by senolytics in animal models. Overall, it is of importance for physicians active in osteology to understand the interrelationships in the development of the high risk of severe COVID-1 disease in our elderly patient cohorts, and also to consider the consequences of severe COVID-19 disease. We also urgently need to pay attention to what e. g. long-covid disease means for existing and emerging musculoskeletal conditions such as osteoporosis and sarcopenia due to prolonged absolute and relative immobilization during the acute and rehabilitation phases. © 2022 Georg Thieme Verlag. All rights reserved.
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Severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2), which causes Coronavirus disease-2019 (COVID-19), has rapidly spread all over the world and has become a public health emergency. Coronavirus disease-2019 has a wide clinical spectrum, from asymptomatic infection to Acute respiratory distress syndrome, sepsis, metabolic acidosis, coagulation disorder, multi-organ failure and even death. The dysregulated and hyperimmune response to SARS-CoV-2 could possibly explain the highly variable disease manifestations and play an important role in the pathogenesis of COVID-19. Since there is no specific antiviral treatment in the treatment of COVID-19, treatments for inflammation against the virus and sharing experience are important. Mesenchymal stem cells (MSCs) have potent anti-inflammatory and immunomodulatory abilities that can migrate to damaged tissues, promote tissue regeneration, and inhibit tissue fibrosis. Today, MSCs are widely used in many clinical studies on immune-mediated inflammatory diseases such as Graft-versus-Host disease, systemic lupus erythematosus, and perianal Crohn's disease. MSC treatment in COVID-19 is a promising option. In this study, we would present four patients with COVID-19 who were treated with MSCs and who were found to be positive for real-time polymerase chain reaction tests on nasopharyngeal swab or tracheal aspirate. All patients were critically ill were followed up with mechanical ventilator due to severe hypoxemia. One patient was extubated and discharged. Other patients died. In this study, MSCs were used as salvage therapy in the late period, so benefit might not be seen. In previous studies, this treatment was used earlier and there were results showing the benefits of MSCs. Based on this study, MSCs can be a promising treatment option when used in the appropriate patient at the appropriate time.
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Exosomes are lipid bilayer-enclosed nano-sized vesicles, which carry various biomolecules including proteins, lipids, and microRNAs. SARS-CoV-2-loaded exosomes can be entered into the susceptible host cells, and transported viral components which are associated with viral particles intercellular transmission and spread of infection. Over-stimulation of the immune system followed by excessive proinflammatory cytokine production is a hallmark of COVID-19. Mesenchymal stem cell-derived exosomes are a potential therapeutic option in COVID-19 due to their ability to decrease cytokine storm, improve tissue regeneration, and prevent multi-organs failure. Unraveling the exact role of exosomes underlying COVID-19 infection will be beneficial in understanding novel aspects of COVID-19 pathogenesis and therapy. This study aimed to investigate the importance of exosomes in COVID-19.