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Stem cells or their exosomes: which is preferred in COVID-19 treatment?

ABSTRACT: It only took 8 months for the pneumonia caused by a previously unknown coronavirus to turn into a global pandemic of unprecedentedly far-reaching implications. Failure of the already discovered treatment measures opened up a new opportunity to evaluate the potentials of mesenchymal stem cells and their extracellular vesicles (EVs), exosomes in particular. Eventually, the initial success experienced after the use of MSCs in treating the new pneumonia by Lnge and his team backed up the idea of MSC-based therapies and pushed them closer to becoming a reality. However, MSC-related concerns regarding safety such as abnormal differentiation, spontaneous malignant and the formation of ectopic tissues have triggered the replacement of MSCs by their secreted exosomes. The issue has been further strengthened by the fact that the exosomes leave similar treatment impacts when compared to their parental cells. In recent years, much attention has been paid to the use of MSC-derived exosomes in the treatment of a variety of diseases. With a primary focus on COVID-19 and its current treatment methods, the present review looks into the potentials of MSCs and MSC-derived exosomes in battling the ongoing pandemic. Finally, the research will draw an analogy between exosomes and their parental cells, when it comes to the progresses and challenges in using exosomes as a large-scale treatment method.

SUBMITTER: Hosseini NF

PROVIDER: S-EPMC8765836 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Immunomodulatory effect of mesenchymal stem cells and mesenchymal stem-cell-derived exosomes for COVID-19 treatment.

Project description:The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].

| S-EPMC7473478 | biostudies-literature

Mesenchymal stem cells and their derived exosomes to combat Covid-19.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an ongoing pandemic of coronavirus disease 2019 (Covid-19). Effective therapies are required for the treatment of patients with severe stages of the disease. Mesenchymal stem cells (MSCs) have been evaluated in numerous clinical trials, but present challenges, such as carcinogenic risk and special storage conditions, coupled with insufficient data about their mechanism of action. The majority of unique properties of MSCs are related to their paracrine activity and especially to their exosomes. The impact of MSCs-derived exosomes (MSC-Es) on complications of Covid-19 has been investigated in several studies. MSC-Es may improve some complications of Covid-19 such as cytokine storm, acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Additionally, these exosomes can be evaluated as an applicable nano-size carrier for antiviral therapeutic agents. Herein, we consider several potential applications of MSCs and their derived exosomes in the treatment of Covid-19.

| S-EPMC8420536 | biostudies-literature

Exosomes contribution in COVID-19 patients' treatment.

Project description:Adipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. In this context, mesenchymal stromal/stem cells (MSCs), adipocyte mesenchymal stem cells (Ad-MSCs) and adipose-derived stem cells (ADSC) possessing potent immunomodulatory activities are proposed as a therapeutic option for the treatment of coronavirus disease 2019 (COVID-19). The COVID-19 represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which there is not actually any specific therapy. MSCs exert an immunomodulation effect due to the secretion of endogenous factors, such as vascular endothelial growth factor (VEGF), insulin growth factor (IGF), and nerve growth factor (NGF), transforming growth factor (TGF)-β and growth differentiation factor (GDF)-11. Recent reports are promising for further studies and clinical applications of ADSCs and Ad-MSCs in COVID-19 patients. Experimental and clinical studies are exploring the therapeutic potential of both MSCs and derived-exosomes in moderating the morbidity and mortality of COVID-19. In this field, more preclinical and clinical studies are warranted to find an effective treatment for the patients suffering from COVID-19 infection.

| S-EPMC8165679 | biostudies-literature

Proposed Mechanisms of Targeting COVID-19 by Delivering Mesenchymal Stem Cells and Their Exosomes to Damaged Organs.

Project description:With the outbreak of coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world has been facing an unprecedented challenge. Considering the lack of appropriate therapy for COVID-19, it is crucial to develop effective treatments instead of supportive approaches. Mesenchymal stem cells (MSCs) as multipotent stromal cells have been shown to possess treating potency through inhibiting or modulating the pathological events in COVID-19. MSCs and their exosomes participate in immunomodulation by controlling cell-mediated immunity and cytokine release. Furthermore, they repair the renin-angiotensin-aldosterone system (RAAS) malfunction, increase alveolar fluid clearance, and reduce the chance of hypercoagulation. Besides the lung, which is the primary target of SARS-CoV-2, the heart, kidney, nervous system, and gastrointestinal tract are also affected by COVID-19. Thus, the efficacy of targeting these organs via different delivery routes of MSCs and their exosomes should be evaluated to ensure safe and effective MSCs administration in COVID-19. This review focuses on the proposed therapeutic mechanisms and delivery routes of MSCs and their exosomes to the damaged organs. It also discusses the possible application of primed and genetically modified MSCs as a promising drug delivery system in COVID-19. Moreover, the recent advances in the clinical trials of MSCs and MSCs-derived exosomes as one of the promising therapeutic approaches in COVID-19 have been reviewed.

| S-EPMC7799400 | biostudies-literature

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.

Project description:BackgroundCOVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19.ObjectivesTo determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19.MethodsPatients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups.Measurements and main resultsThe incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group.ConclusionsIntravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.Trial registrationChinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.

| S-EPMC7432540 | biostudies-literature

The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes as Immunomodulatory Agents for COVID-19 Patients.

Project description:A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing lethal acute respiratory disease emerged in December 2019. The World Health Organization named this disease "COVID-19" and declared it a pandemic on March 11, 2020. Many studies have shown that mesenchymal stem cells (MSCs) and their exosomes (MSCs-Exo), which are isolated from allogenic bone marrow stem cells, significantly lower the risk of alveolar inflammation and other pathological conditions associated with distinct lung injuries. For example, in acute respiratory distress syndrome (ARDS) and pneumonia patients, MSCs-Exo and MSCs provide similar healing properties and some clinical trials have used cell-based inhalation therapy which show great promise. MSCs and MSCs-Exo have shown potential in clinical trials as a therapeutic tool for severely affected COVID-19 patients when compared to other cell-based therapies, which may face challenges like the cells' sticking to the respiratory tract epithelia during administration. However, the use of MSCs or MSCs-Exo for treating COVID-19 should strictly adhere to the appropriate manufacturing practices, quality control measurements, preclinical safety and efficacy data, and the proper ethical regulations. This review highlights the available clinical trials that support the therapeutic potential of MSCs or MSCs-Exo in severely affected COVID-19 patients.

| S-EPMC7512102 | biostudies-literature

Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases.

Project description:The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

| S-EPMC7306412 | biostudies-literature

Mesenchymal Stem Cell-Derived Exosomes for COVID-19 Therapy, Preclinical and Clinical Evidence.

Project description:Since the emergence of the novel coronavirus, named COVID-19, researchers are looking for a treatment to stop the devastating pandemic. During these efforts, mesenchymal stem cells (MSCs), the potential next generation of therapeutic methods with wide application for diseases, have successfully controlled cytokine storm following the virus infection. However, the use of MSCs has been limited due to the ethical issues, immunogenicity, and genetic modifications. Therefore, exosomes were introduced as a suitable substitute for the MSCs. In the case of COVID-19 treatment, both MSCs and exosomes exert their beneficial effect mainly through the management of the cytokine storm. This study provided the underlying mechanisms for the effect of exosomes on COVID-19 treatment and presented several preclinical and clinical studies of exosomes for COVID-19 treatment.

| S-EPMC8429942 | biostudies-literature

Mesenchymal Stem Cells: A New Piece in the Puzzle of COVID-19 Treatment.

Project description:COVID-19 is a disease characterized by a strong inflammatory response in severe cases, which fails to respond to corticosteroid therapy. In the context of the current COVID-19 outbreak and the critical information gaps regarding the disease, several different therapeutic strategies are under investigation, including the use of stem cells. In the present manuscript, we provide an analysis of the rationale underlying the application of stem cells to manage COVID-19, and also a comprehensive compendium of the 69 clinical trials underway worldwide aiming to investigate the application of stem cells to treat COVID-19. Even though data are still scarce, it is already possible to observe the protagonism of China in testing mesenchymal stem cells (MSCs) for COVID-19. Furthermore, it is possible to determine that current efforts focus on the use of multiple infusions of high numbers of stem cells and derived products, as well as to acknowledge the positive results obtained by independent groups who publicized the therapeutic benefits provided by such therapies in 51 COVID-19 patients. In such a rapid-paced field, up-to-date systematic studies and meta-analysis will aid the scientific community to separate hype from hope and offer an unbiased position to the society and governments.

| S-EPMC7347794 | biostudies-literature

Decreased memory B cells frequencies in COVID-19 Delta variant vaccine breakthrough infection

Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.

| S-SCDT-EMM-2021-15227 | biostudies-other

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