Molecular investigation of adequate sources of mesenchymal stem cells for cell therapy of COVID-19-associated organ failure.
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ABSTRACT:
SUBMITTER: Desterke C
PROVIDER: S-EPMC7753753 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.
| S-EPMC8616204 | biostudies-literature
Project description:Mesenchymal stem/stromal cells (MSCs)-based therapy brings the reassuring capability to regenerative medicine through their self-renewal and multilineage potency. Also, they secret a diversity of mediators, which are complicated in moderation of deregulated immune responses, and yielding angiogenesis in vivo. Nonetheless, MSCs may lose biological performance after procurement and prolonged expansion in vitro. Also, following transplantation and migration to target tissue, they encounter a harsh milieu accompanied by death signals because of the lack of proper tensegrity structure between the cells and matrix. Accordingly, pre-conditioning of MSCs is strongly suggested to upgrade their performances in vivo, leading to more favored transplantation efficacy in regenerative medicine. Indeed, MSCs ex vivo pre-conditioning by hypoxia, inflammatory stimulus, or other factors/conditions may stimulate their survival, proliferation, migration, exosome secretion, and pro-angiogenic and anti-inflammatory characteristics in vivo. In this review, we deliver an overview of the pre-conditioning methods that are considered a strategy for improving the therapeutic efficacy of MSCs in organ failures, in particular, renal, heart, lung, and liver.
| S-EPMC10249180 | biostudies-literature
Project description:The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in December 2019 and affected the whole world in a short time. The course of the disease depends on the person's immune system, physical properties, health status, etc. as it varies according to its characteristics while it is asymptomatic in some people, it causes fatal processes that start with flu-like symptoms such as cough, fever, respiratory distress in some people and progress to acute respiratory distress syndrome (ARDS), severe pneumonia and multi-organ dysfunction, and the basic mechanism underlying these effects known as a cytokine storm. There is no specific effective antiviral drug or vaccine in treatment yet. Supportive/alternative treatment methods are needed as both the desired effect cannot be achieved and undesirable side effects are seen with the current treatments used in the clinic. Mesenchymal stem cells (MSCs) are frequently preferred recently from basic studies to clinical studies and are effective and safe in immune-mediated inflammatory diseases such as Systemic Lupus Erythematosus, Graft-versus-Host disease. MSCs can secrete many types of cytokines through paracrine secretion or directly interact with immune cells leading to immunomodulation. According to the results of the completed studies; it has been stated that the cytokine storm caused by the overstimulation of the immune system decreases and even damage of the cytokine storm on organs decreases, respiratory distress is relieved and contributes to the healing process by repairing damaged tissues. In this review, clinical trials completed/ongoing on MSCs recommended for treating COVID-19, a global problem, are reviewed and the review is prepared to specify the existence of such a route to clinicians.
| S-EPMC8784829 | biostudies-literature
Project description:Precise reasons for severe manifestation of SARS-CoV-2 remain unanswered, and efforts have been focused on respiratory system management. Demonstration of unequivocal presence of SARS-CoV-2 in vital body organs by cadaver autopsy was the only way to prove multi-organ involvement. Hence, the primary objective of the study was to determine presence of the SARS-CoV-2 in various organs of patients succumbing to SARS-CoV-2 infection. A total of 246 samples from different organs of 21 patients who died due to severe COVID-19 illness were investigated by qRT-PCR, and SARS-CoV-2 was detected in 181 (73.57%) samples and highest positivity of SARS-CoV-2 being (expectedly) found in nasopharynx (90.4%) followed by bilateral lungs (87.30%), peritoneal fluid (80%), pancreas (72.72%), bilateral kidneys (68.42%), liver (65%) and even in brain (47.2%). The deceased patients were categorized to three subgroups based upon the extent of organs in which SARS-CoV-2 was detected by qRT-PCR (high intensity ≥80%, intermediate intensity = 65–80% and low intensity ≤65% organs involvement). It was conclusively established that SARS-CoV-2 has the property of invasion beyond lungs and even crosses the blood–brain barrier, resulting in multi-system disease; this is probably the reason behind cytokine storm, though it is not clear whether organ damage is due to direct injury caused by the virus or result of inflammatory assault. Significant inverse correlation was found between the Ct value of lung samples and number of organs involved, implying that higher viral load in lungs is directly proportionate to involvement of extrapulmonary organs and patients with higher viral load in respiratory secretions should be monitored more closely for any warning signs and the treatment strategies should also address involvement of other organs for better outcome, because lungs, though the primary site of infection, are not the only organ system responsible for pathogenesis of systemic illness.
| S-EPMC9318581 | biostudies-literature
Project description:The COVID-19 disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it's initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.
| S-EPMC7224671 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.
| S-EPMC8424619 | biostudies-literature
Project description:The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) are currently utilized in clinics for pulmonary inflammatory diseases, including acute respiratory distress syndrome and acute lung injury. Given that MSCs offer a promising treatment against COVID-19, they are being used against COVID-19 in more than 70 clinical trials with promising findings. Genetically engineered MSCs offer promising therapeutic options in pulmonary diseases. However, their potential has not been explored yet. In this review, we provide perspectives on the functionally modified MSCs that can be developed and harnessed for COVID-19 therapy. Options to manage the SARS-CoV-2 infection and its variants using various bioengineering tools to increase the therapeutic efficacy of MSCs are highlighted.
| S-EPMC8834073 | biostudies-literature
Project description:"COVID-19" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.
| S-EPMC7152513 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) global pandemic continues and antiviral agents and vaccines are currently under investigation. Mesenchymal stem cell (MSC)-based therapy can be a suitable option for management of patients with COVID-19 at the urgent time of virus outbreak. Currently, MSCs are being explored against the novel infectious disease due to their therapeutic properties of anti-inflammation, immunomodulation and tissue repair and regeneration, albeit the precise mechanisms of MSC action toward COVID-19 remain unclear. To date, rigorous results from clinical trials using MSCs in human have been weakly positive. The pervasive uncertainty of using MSC therapeutic products as an effective combatant against COVID-19 requires rigorous resolution on several fronts, including MSC fate after infusion, safety issue, homing capability, and MSC resistance to the disease microenvironment. Focusing on these facets, a few important ones will be critically analyzed and addressed in this article for the development of safe and effective MSC-based therapies for COVID-19.
| S-EPMC7533900 | biostudies-literature
Project description:The large economic burden on the global health care systems is due to the increasing number of symptomatic osteoarthritis (OA) knee patients whereby accounting for greater morbidity and impaired functional quality of life. The recent developments and impulses in molecular and regenerative medicine have paved the way for inducing the biological active cells such as stem cells, bioactive materials, and growth factors towards the healing and tissue regenerative process. Mesenchymal stem cells (MSCs) act as a minimally invasive procedure that bridges the gap between pharmacological treatment and surgical treatment for OA. MSCs are the ideal cell-based therapy for treating disorders under a minimally invasive environment in conjunction with cartilage regeneration. Due to the worldwide recognized animal model for such cell-based therapies, global researchers have started using the various sources of MSCs towards cartilage regeneration. However, there is a lacuna in literature on the comparative efficacy and safety of various sources of MSCs in OA of the knee. Hence, the identification of a potential source for therapeutic use in this clinical scenario remains unclear. In this article, we compared the therapeutic effects of various sources of MSCs in terms of efficacy, safety, differentiation potential, durability, accessibility, allogenic preparation and culture expandability to decide the optimal source of MSCs for OA knee.
| S-EPMC8327191 | biostudies-literature