Gene Context Sentence

Table 2. Analysis of context sentence of MSC gene in 78 abstracts.

PMID Gene Context Sentence
32214286 Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. […] Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. […] The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. […] The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis…1.
32257537 Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. […] This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. […] The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. […] MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. […] The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. […] Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. […] Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. […] Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
32257554 A new study published by the journal Aging & Disease reported that intravenous administration of clinical-grade human mesenchymal stem cells (MSCs) into patients with coronavirus disease 2019 (COVID-19) resulted in improved functional outcomes (Leng et al., Aging Dis, 11:216-228, 2020). […] This study demonstrated that intravenous infusion of MSCs is a safe and effective approach for treating patients with COVID-19 pneumonia, including elderly patients displaying severe pneumonia. […] Therefore, MSC therapy inhibiting the overactivation of the immune system and promoting endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection found in this study is striking.
32265310 Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), although not as yet well studied in respiratory virus-induced ARDS. […] Limited pre-clinical data suggest that systemic MSC administration can significantly reduce respiratory virus (Influenza strains H5N1 and H9N2)-induced lung injury, however, there are no available data in models of coronavirus respiratory infection.There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. […] To provide a rationale strategy to maximise potential therapeutic use, it is critically important to understand the relevant pre-clinical studies and postulated mechanisms of MSC actions in respiratory virus-induced lung injuries.
32281052 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. […] 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.
32292627 Transplantation of mesenchymal stem cells (MSCs) is a promising choice for treating virus-induced pneumonia, and was needed to treat H7N9 induced ARDS at the time. […] MSCs transplant into patients with H7N9 induced ARDS were conducted in a single center and open-label clinical trial. […] Based on the principle of voluntariness and informed consent, 44 patients with H7N9 induced ARDS were included as a control group while 17 patients with H7N9 induced ARDS were served as an experimental group with allogeneic menstrual blood-derived MSC. […] Notably, MSC transplantation significantly lower the mortality compared with in control group (17.6% died in MSC group vs 54.5% died in control group). […] Furthermore, MSC transplantation did not result in harmful effects in human body within the 5 year follow up period with 4 patients. […] Collectively, these results suggest that MSCs significantly improve survival rate of H7N9 induced ARDS and provide a theoretical basis for the treatment of H7N9 induced ARDS in both preclinical research and clinical studies. […] Because H7N9 and the corona virus disease 2019 (COVID-19) share similar complications (such as ARDS and lung failure) and corresponding multi-organ dysfunction, MSC-based therapy could be a possible alternative for treating COVID-19.
32371362 We have previous evidence in murine models that MSc’s secretome can be used to treat pulmonary injuries induced with bleomycin, due to its content: growth factors, extracellular vesicles, and exosomes. […] We hypothesize and strongly recommend MSc secretome testing and production, in xenofree conditions, to be used as an alternative approach in SARS-Cov-2 patients in critical conditions.
32423449 Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. […] Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC’s impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. […] Additionally, MSCs produce molecules that are antimicrobial and reduce pain. […] The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). […] Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. […] Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality.
32425638 We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. […] MSCs should also be trialed for treatment of severe cases of MERS where mortality rates are upto 34% and MERS-CoV remains a WHO priority Blueprint pathogen. […] It’s about time funding agencies now invest more into development MSCs per se and other host-directed therapies in combination with other therapeutic interventions. […] MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 and MERS death rates.
32449333 Similarly, the use of mesenchymal stem cells (MSC) may assist the body regulatory mechanisms, knowing the anti-inflammatory potential of these cells.
32472653 Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. […] The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. […] MSCs were intravenously or intratracheally administered in 200 participants, who were followed for 14 days to 5 years. […] All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. […] No comparisons were made between MSCs of different sources.
32489694 Mesenchymal stem cells (MSCs) bear a promising potential for regenerative medicine therapies and they repair damaged tissue through secretion of immune modulatory and anti-inflammatory molecules acting in a paracrine fashion. […] A recent study published in the journal reports that MSC infusion is safe and effective in patients suffering from COVID-19 induced pneumonia. […] In the light of this study and previous reports, we make additional comments about possible therapeutic effects of MSCs in COVID-19 infection.
32519302 Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. […] By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. […] An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. […] Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. […] Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
32526079 The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) has allowed for wide application in regenerative medicine as well as immune/inflammatory diseases, including unmatched allogeneic use. […] Since there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID-19. […] Interestingly, MSCT preclinical data specifically on immune/inflammatory disorders of the lungs were among the earliest to be reported in 2003, with the first clinical use of MSCT for graft-vs-host disease reported in 2004. […] Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. […] There is much preclinical evidence for MSCT in noninfectious-including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis-as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. […] In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials-including for COVID-19-of MSCT for these diseases, with some perspectives and comment on MSCT for COVID-19.
32554953 To combat cytokine storm, immune-therapy targeting IL-1, IL-2, IL-6 and TNFα are being evaluated and one of the promising immune-modulator is the mesenchymal stem cells (MSCs) that can surmount the severity of COVID-19 infections. […] Recent studies have shown that MSC-therapy significantly dampens the cytokine storm in critically ill COVID-19 patients.
32562911 One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). […] MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. […] MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. […] But our suggestion is using MSCs-derived exosomes. […] Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don’t have problems associated to cell maintenance and injections. […] For investigation the hypothesis, MSCs should be isolated from tissues and characterized.
32574263 Numerous clinical trials of mesenchymal stromal/stem cells (MSCs) as a new treatment for coronavirus-induced disease (COVID-19) have been registered recently, most of them based on intravenous (IV) infusion. […] There is no approved effective therapy for COVID-19, but MSC therapies have shown first promise in the treatment of acute respiratory distress syndrome (ARDS) pneumonia, inflammation, and sepsis, which are among the leading causes of mortality in COVID-19 patients. […] It is not yet clear whether IV infusion is a safe and effective route of MSC delivery in COVID-19, since MSC-based products express variable levels of highly procoagulant tissue factor (TF/CD142), compromising the cells’ hemocompatibility and safety profile. […] Of concern, IV infusions of poorly characterized MSC products with unchecked (high) TF/CD142 expression could trigger blood clotting in COVID-19 and other vulnerable patient populations and further promote the risk for thromboembolism. […] While the need for MSC therapy in COVID-19 is apparent, integrating both innate and adaptive immune compatibility testing into the current guidelines for cell, tissue, and organ transplantation is critical for safe and effective therapies. […] It is paramount to only use well-characterized, safe MSCs even in the most urgent and experimental treatments.
32574317 In this review article, we outline the mechanisms of cytokine storm and lung damage caused by SARS-CoV-2 virus leading to COVID-19 disease and how mesenchymal stem cells (MSCs) and their secreted EVs can be utilized to tackle this damage by harnessing their regenerative properties, which gives them potential enhanced clinical utility compared to other investigated pharmacological treatments. […] There are currently 17 clinical trials evaluating the therapeutic potential of MSCs for the treatment of COVID-19, the majority of which are administered intravenously with only one clinical trial testing MSC-derived exosomes via inhalation route.
32582401 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. […] 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
32595362 Mesenchymal stem/stromal cells (MSCs), highly regarded for their regenerative capacities, also possessesremarkable immunoregulatory functions affecting all types of innate and adaptive immune cells. […] Owing to that, MSCs have been heavily investigated in clinic for the treatment of autoimmune and inflammatory diseases along with transplant rejection. […] Extensive research in the last decaderevealed that MSCs carry out most of their functions through paracrine factors which are soluble mediators and extracellular vesicles (EVs). […] EVs secreted by MSCs are emerging as a cell-free alternative to MSC-based therapies. […] MSC EVs are being tested in preclinical and clinical settings where they exhibit exceptional immunosuppressivecapacity. […] Being as effective immunomodulators as their parent cells, MSC EVs are also preferable over MSC-based therapies due to their lower risk of immunogenicity, tumorigenicity and overall superior safety. […] In this review, we present the outcomes of preclinical and clinical studies utilizing MSC EVs as therapeutic agents for the treatment of a wide variety of immunological disorders.
32616467 The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. […] In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. […] However, the potential of MSCs to control or treat viral diseases is still in its infancy. […] In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. […] In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.
32622963 Mesenchymal stem/stromal cells (MSCs) have been tested during the last two decades for the treatment of various pathologic conditions, including acute and chronic lung diseases, both in animal models and in patients. […] Furthermore, more recently, great interest has been devoted to the possible clinical applications of extracellular vesicles secreted by MSCs, nanoparticles that convey much of the biological effects and of the therapeutic efficacy of their cells of origin. […] This review summarizes the experimental evidence underlying the possible use of MSCs and of MSC-EVs in severe COVID-19 infection and underlines the need to evaluate the possible efficacy of these therapeutic approaches through controlled studies under the supervision of the Regulatory Authorities.
32731913 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.
32740890 Mesenchymal stem cell (MSC) therapy has been shown to alleviate pneumonia and acute respiratory syndrome (ARDS) symptoms, through their immunomodulatory activities in COVID-19 patients. […] Although more research studies and clinical trial results are needed to elucidate the exact mechanism by which MSCs provide relief to COVID-19 infected patients. […] Results from clinical trials are encouraging as patients treated with MSCs, regain lung functions and have restored levels of cytokines and trophic factors underscoring the fact that stem cell therapy can be, at least, a complementary therapy to alleviate sufferings in COVID-19 patients. […] This review discusses the possible therapeutic uses of MSCs for treating COVID-19.
32755466 The mesenchymal stem cell (MSC), known to remodel in disease and have an extensive secretome, has recently been isolated from the human heart. […] However, the effects of normal and diseased cardiac MSCs on myocyte electrophysiology remain unclear. […] We hypothesize that in disease the inflammatory secretome of cardiac human MSCs (hMSCs) remodels and can regulate arrhythmia substrates. hMSCs were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted/donor hearts. […] Failing hMSCs or nonfailing hMSCs were cocultured with normal human cardiac myocytes derived from induced pluripotent stem cells. […] Failing and nonfailing hMSCs from both sources exhibited similar trilineage differentiation potential and cell surface marker expression as bone marrow hMSCs. […] Compared with nonfailing hMSCs, failing hMSCs prolonged action potential duration by 24% (P<0.001, n=15), increased Ca2+ alternans by 300% (P<0.001, n=18), and promoted spontaneous calcium release activity (n=14, P<0.013) in human cardiac myocytes derived from induced pluripotent stem cells. […] Failing hMSCs exhibited increased secretion of inflammatory cytokines IL (interleukin)-1β (98%, P<0.0001) and IL-6 (460%, P<0.02) compared with nonfailing hMSCs. […] IL-1β or IL-6 in the absence of hMSCs prolonged action potential duration but only IL-6 increased Ca2+ alternans and promoted spontaneous calcium release activity in human cardiac myocytes derived from induced pluripotent stem cells, replicating the effects of failing hMSCs. […] In contrast, nonfailing hMSCs prevented Ca2+ alternans in human cardiac myocytes derived from induced pluripotent stem cells during oxidative stress. […] Finally, nonfailing hMSCs exhibited >25× higher secretion of IGF (insulin-like growth factor)-1 compared with failing hMSCs. […] Importantly, IGF-1 supplementation or anti-IL-6 treatment rescued the arrhythmia substrates induced by failing hMSCs. […] We identified device leads as a novel source of cardiac hMSCs. […] Our findings show that cardiac hMSCs can regulate arrhythmia substrates by remodeling their secretome in disease. […] Importantly, therapy inhibiting (anti-IL-6) or mimicking (IGF-1) the cardiac hMSC secretome can rescue arrhythmia substrates.
32761491 Mesenchymal stem cell (MSC) therapy is the immediate treatment used for patients with severe cases of COVID-19. […] Herein, we describe two confirmed cases of COVID-19 in Wuhan to explore the role of MSC in the treatment of COVID-19. […] MSC transplantation increases the immune indicators (including CD4 and lymphocytes) and decreases the inflammation indicators (interleukin-6 and C-reactive protein). […] With MSC transplantation, the fraction of inspired O2 (FiO2) of the two patients gradually decreased while the oxygen saturation (SaO2) and partial pressure of oxygen (PO2) improved. […] Additionally, the patients’ chest computed tomography showed that bilateral lung exudate lesions were adsorbed after MSC infusion. […] Results indicated that MSC transplantation provides clinical data on the treatment of COVID-19 and may serve as an alternative method for treating COVID-19, particularly in patients with ARDS.
32766251 Mesenchymal (stem) stromal cells (MSC) can be a therapeutic alternative for COVID-19 considering their anti-inflammatory, regenerative, angiogenic, and even antimicrobial capacity. […] Preliminary data point to therapeutic interest of MSC for patients with COVID-19, and their effect seems based on the MSC’s ability to curb the cytokine storm caused by COVID-19. […] In fact, promising clinical studies using MSC to treat COVID-19, are currently underway. […] For this reason, now is the time to firmly consider new approaches to MSC research that addresses key issues, like selecting the most optimal type of MSC for each indication, assuming the heterogeneity of the donor-dependent MSC and the biological niche where MSC are located.
32779878 Given that human mesenchymal stem cells (MSCs) from various tissue sources have revealed successful clinical outcomes in many immunocompromised disorders by inhibiting the overactivation of the immune system and promoting endogenous repair by improving the microenvironment, there is a growing demand for MSC infusions in patients with COVID-19-related ARDS in the ICU. […] In this review, we have documented the rationale and possible outcomes of compassionate use of MSCs, particularly in patients with SARS-CoV-2 infections, toward proving or disproving the efficacy of this approach in the near future.
32795359 Mesenchymal stem cell-derived exosomes (MSC-Exo) are believed to have anti-inflammatory effects and immune-modulating capacity as well as the ability to induce tissue regeneration, suggesting a significant therapeutic opportunity that could be used to SARS-CoV-2 pneumonia treatment. […] MSC-Exo may serve as a promising tool in the treatment of SARS-CoV-2 pneumonia.
32811531 Patients 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 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. […] 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. […] Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.
32820868 To date, numerous studies have been conducted to evaluate the safety and efficacy of tissue engineering and regenerative medicine (TERM) products, including mesenchymal stem cells (MSCs), and their derivatives (eg, exosomes) for coronavirus infections, which could be applied for the COVID-19. […] Then, the recent clinical trials and the therapeutic benefits of MSCs in coronavirus-induced ARDS are critically reviewed. […] Despite promising results in the preclinical and clinical applications of MSC therapy for coronavirus infections, the controversy still exists, and thus further investigation is required to understand the efficacy of these therapies.
32825283 Fortunately, some novel antiviral strategies, such as convalescent plasma, clustered regularly interspaced short palindromic repeats (CRISPR), and mesenchymal stem cell (MSC) therapy, potentially offer an additional or alternative option or compassionate use for the people suffering from COVID-19, especially for critically ill patients, although their safety and efficacy are also under study. […] In this review, we explore the applications, possible mechanisms, and efficacy in successful cases using convalescent plasma, CRISPR, and MSC therapy for COVID-19 treatment, respectively.
32827081 Basically, the ongoing studies on coronavirus are using mesenchymal stem cells (MSCs) derived from bone marrow or the umbilical cord to demonstrate their feasibility, safety, and tolerability. […] With the COVID-19 boom, many clinical trials are being carried out using different sources with an emphasis on MSC-based therapy used to inhibit inflammation. […] One of the biggest challenges in the current treatment of COVID-19 is the cytokine storm, however MSCs can prevent or mitigate this cytokine storm through their immunomodulatory capacity.
32830527 Mesenchymal stem cells (MSCs) are known to act as anti-inflammatory/immunomodulatory candidates and activate endogenous regeneration. […] As a result, MSC therapy is a potential treatment approach for COVID-19. […] Intravenous injection of clinical-grade MSCs into COVID-19 patients can induce an immunomodulatory response along with improved lung function. […] Dental pulp stem cells (DPSCs) are considered a potential source of MSCs for immunomodulation, tissue regeneration, and clinical application.
32832666 More than 1050 clinical trials are registered at that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. […] Several companies have or are in the process of commercializing MSC-based therapies. […] However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. […] The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. […] In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.
32835174 Marten holds a MSc in Economics, a MSc in Energy Engineering, and a PhD in Economics from KU Leuven.
32838232 Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. […] Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. […] Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient’s body weight. […] First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. […] Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). […] Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. […] Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.
32854985 Mesenchymal stromal cells (MSC) have immune regulatory and tissue regenerative properties. […] MSCs are being studied as a therapy option for many inflammatory and immune disorders and are approved to treat acute graft-versus-host disease (GvHD). […] Preliminary data using MSCs in the setting of acute respiratory distress syndrome (ARDS) in COVID-19 are emerging. […] We review mechanisms of action of MSCs in inflammatory and immune conditions and discuss a potential role in persons with COVID-19.
32858940 Exosomes derived from mesenchymal stem cells (MSCs) are being explored for the management of a number of diseases that currently have limited or no therapeutic options, thanks to their anti-inflammatory, immunomodulatory, and pro-angiogenic properties. […] Next, we describe some of the most significant clinical evidence of the successful use of MSC-derived exosomes in animal models of lung and heart injuries, which might strengthen our hypothesis in terms of their utility for also treating critically ill COVID-19 patients.
32895900 Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. […] MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. […] To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. […] Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. […] Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (COVID-19). […] Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. […] MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. […] We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. […] Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.
32933835 Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. […] According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. […] Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately.
32942796 Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore the function of damaged tissues and organs. […] To date, there has been no review of all the clinical trials that have assessed the safety and efficacy of MSC therapy in organ failure commonly seen in seriously complicated COVID-19 patients. […] To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature. […] A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing multiorgan failure. […] Studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. […] Trials with intraorgan infiltration of MSC were also excluded. […] The secondary outcome assessed the safety of MSC therapy in the clinical trials. […] Among the 6 studies that specifically assessed the effectiveness of MSC therapy in ARDS, 4 showed positive outcomes. […] The incidence of disease worsening or major complications was extremely rare from MSC therapy. […] MSC therapy seems to be promising to treat multiorgan failure from COVID-19.
32942797 This review examines recent research studies in humans to determine whether mesenchymal stem cells (MSCs) may be used effectively and safely to target potentially deadly lung damage that may follow infection. […] Electronic data bases of scientific articles and records of printed documents of JAMA journals were searched to find research publications on MSC treatment of ARDS and COVID-19. […] Two randomized double-blind clinical trials, 2 pilot studies, and 2 case reports described MSC use to treat ARDS with specific focus on COVID-19 and lung symptoms of cytokine storm. […] The MSCs were well-tolerated across studies. […] No significant differences in treatment outcome were found in randomized double-blind trials; however, results of 1 pilot study and 1 case report showed that MSCs led to lung symptom resolution and survival in severely ill treatment patients. […] Nevertheless, it is documented that 8 ARDS patients with COVID-19 experienced symptom recovery and survival subsequent to MSC administration. […] MSCs are potentially life-saving treatment approaches for some patients who exhibit severe lung distress and have not responded to standard treatments.
32948252 Mesenchymal stem cells (MSCs) are multipotential stem cells that are recognized via self-renewal capacity, generation of clonal populations, and multilineage differentiation. […] MSCs are present in nearly all tissues of the body, playing an essential role in repair and generation of tissues. […] Furthermore, MSCs have broad immunoregulatory properties through the interaction of immune cells in both innate and adaptive immune systems, leading to immunosuppression of many effector activities. […] MSCs can reduce the cytokine storm produced by coronavirus infection. […] Also, MSCs may be able to improve pulmonary fibrosis and lung function. […] In this review, we will review the newest research findings regarding MSC-based immunomodulation in patients with COVID-19.
32952855 Mesenchymal stromal cells (MSCs), which are known for their immunosuppressive actions, could be applied as an alternative co-therapy in critically-ill COVID-19 patients. […] Specifically, MSCs can regulate the immune responses through the conversion of Th1 to Th2, activation of M2 macrophages, and modulation of dendritic cells maturation. […] These key immunoregulatory properties of MSCs may be exerted either by produced soluble factors or by cell-cell contact interactions. […] To date, several clinical trials have been registered to assess the safety, efficacy, and therapeutic potential of MSCs in COVID-19. […] Moreover, MSC treatment may be effective for the reversion of ground-glass opacity of damaged lungs and reduce the tissue fibrosis. […] Taking into account the multifunctional properties of MSCs, the proposed stem-cell-based therapy may be proven significantly effective in critically-ill COVID-19 patients.
32979360 Mesenchymal stem cells (MSCs) are widely used in basic science and in a variety of clinical trials. […] MSCs are able to engraft to the damaged tissues after transplantation and promote tissue regeneration, besides MSCs able to secrete immunomodulatory factors that suppress the cytokine storms. […] Moreover, the contribution of MSCs to prevent cell death and inhibit tissue fibrosis is well established. […] In the current review article, the potential mechanisms by which MSCs contribute to the treatment of COVID-19 patients are highlighted. […] Also, current trials that evaluated the potential of MSC-based treatments for COVID-19 are briefly reviewed.
33009982 Mesenchymal stem cells (MSCs) due to their pro/anti-inflammatory and immune-modulatory behavior, Natural Killer (NK) cells thanks to their capacity of lysing virus-infected cells and regulate the resulting immune response, Dendritic cells thanks to immunotherapy and cell-based vaccine engineering, SARS-CoV2-specific T cells due to stimulate and promote the immune system and MSC-derived exosomes because of cell-free therapy and beneficial manufacturing aspects, hold great promises for cell-based therapy applications for treating COVID-19 and similar viral infections. […] Moreover, recently, an innovative approach to COVID-19 based on engineered human MSC has been introduced, which is continuously evacuated and degraded by the body’s immune system during the antigen recognition process.
33037446 Over the last two decades, mesenchymal stromal cells (MSCs) have been the focus of intense research by acadaemia and industry due to their unique features. […] MSCs can be easily isolated and expanded through in vitro culture by taking full advantage of their self-renewing capacity. […] In addition, MSCs exert immunomodulatory effects and can be differentiated into various lineages, which makes them highly attractive for clinical applications in cell-based therapies. […] In this review, we attempted to provide a historical overview of bone marrow history, MSC discovery, characterization, and the first clinical studies conducted.
33049279 Mesenchymal stem cells own self-renewal, differentiation, homing, immunomodulation and remains unaffected by the coronavirus on the virtue of the absence of ACE-2 receptors, indicating that MSC’s could be used an ameliorative approach for COVID-19. […] MSCs have shown to combat the disease via various pathways such as repairing the lung epithelial and endothelial cells, reducing hyperimmune response, maintaining the renin-angiotensin system. […] Although MSCs-based treatment approaches for COVID-19 is still under consideration with limited data, many human clinical trials of MSC’s has been initiated to explore their potential for COVID 19 treatment. […] The current review summarizes and emphasizes on how MSC’s modulate the immune response, can repair the lungs from the impact of the virus, and various aspects of MSC’s as a remedial source for COVID-19, to provide better insight for biomedical researchers and for those who are fascinated by stem cells as a therapeutic approach.
33059757 Mesenchymal stem cells (MSCs) have been proposed as an emerging therapeutic option for the SARS-CoV-2 infection. […] Recently, numerous clinical trials have been registered to examine the safety and efficacy of different types of MSCs and their exosomes for treating COVID-19 patients, with less published data on the mechanism of action. […] Although there is no approved effective therapy for COVID-19 as of yet, MSC therapies showed an improvement in the treatment of some COVID-19 patients. […] MSC’s therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear. […] The use of poorly characterized MSC products remains one of the most significant drawbacks of MSC-based therapy, which could theoretically promote the risk for thromboembolism. […] Optimizing the clinical-grade production of MSCs and establishing a consensus on registered clinical trials based on cell-product characterization and mode of delivery would aid in laying the foundation for a safe and effective therapy in COVID-19. […] In this review, we shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. […] We further highlight the challenges and opportunities in the use of MSC-based therapy.
33061304 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.
33061476 We reported the treatment process and clinical outcome of a 48-year-old man critically ill COVID-19 patient who received transfusion of allogenic human umbilical cord mesenchymal stem cells (UC-MSCs). […] We proposed that UC-MSC transfusion might be a new option for critically ill COVID-19. […] Although only one case we were shown, more similar clinical cases are inquired for further evidence providing the potential effectiveness of UC-MSC treatment.
33098357 Of all the stem cell therapies touted for COVID-19 treatment, mesenchymal stem cells (MSCs) or MSC-like derivatives have been the most promising in preclinical studies and clinical trials so far. […] MSCs have been suggested to ameliorate the cytokine release syndrome (CRS) and protect alveolar epithelial cells by secreting many kinds of factors, demonstrating safety and possible efficacy in COVID-19 patients with acute respiratory distress syndrome (ARDS).
33110915 We performed mesenchymal stem cell (MSC) transplantation considering the signs showing persistent excessive immune response and deterioration despite all supportive and drug therapies. […] The use of MSC therapy may be considered for compassionate use in selected patients.
33172313 : MSC products present considerable therapeutic promise for ARDS and sepsis. […] Optimization of MSC function in preclinical models of ARDS and sepsis has enhanced their beneficial effects. […] MSC-derived products, as cell-free alternatives, may provide further advantages in this field. […] These strategies present opportunity for the clinical development of MSCs and MSC-derived products with enhanced therapeutic efficacy.
33178392 While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. […] Here we discuss the unique ability of MSCs, to act as a “living anti-inflammatory”, which can “rebalance” the cytokine/immune responses to restore equilibrium. […] We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.
33237619 The use of mesenchymal stem cells (MSC) derived from several sources as a major anti-inflammation strategy has been suggested in the recent outbreak of Coronavirus-19 (COVID-19). […] As the virus enters the target cells through the receptor ACE2, it is important to determine if the MSC population transfused to patients could also be a target for the virus entry. […] We report here that ACE2 is highly expressed in adult bone marrow, adipose tissue or umbilical cord-derived MSC. […] On the other hand, placenta-derived MSC express low levels of ACE2 but only in early passages of cultures. […] MSC derived from human embryonic stem cell (hESC) or human induced pluripotent stem cells (hIPSC) express also very low levels of ACE2. […] The transcriptome analysis of the MSCs with lowest expression of ACE2 in fetal-like MSCs is found to be associated in particularly with an anti-inflammatory signature. […] These results are of major interest for designing future clinical MSC-based stem cell therapies for severe COVID-19 infections.
33238848 Since mid-February, therapies involving mesenchymal stem/stromal cells (MSCs) have been proposed for the treatment of patients with COVID-19. […] In light of these recent developments this review will focus on: i) the mechanism of SARS-CoV-2 action and the subsequent pathology in COVID-19, ii) the proposed mechanism(s) of outcome-improving action of MSCs or MSC-derived extracellular vesicles in COVID-19 pneumonia, iii) registered MSC-based clinical trials and interventions for the treatment of COVID-19, iv) published case studies/series/trials reporting the use of MSC-based treatments in COVID-19 cases, and finally v) the need for authority regulations and clinical guidelines for MSC-based treatment strategies for COVID-19.
33249285 Furthermore, the mesenchymal stem cells (MSC) exposed to HPC show improvement of their regenerative capacities and increases the effectiveness of stem cell therapy in different pathologies, including COVID-19.
33274176 Due to their potent immuno- and angiomodulatory characteristics, mesenchymal stem cells (MSCs) may increase oxygen supply in the lungs and may efficiently alleviate ongoing lung inflammation, including SARS-CoV-2-induced ARDS. […] In this review article, we described molecular mechanisms that are responsible for MSC-based modulation of immune cells which play a pathogenic role in the development of SARS-CoV-2-induced ARDS and we provided a brief outline of already conducted and ongoing clinical studies that increase our understanding about the therapeutic potential of MSCs and their secretome in the therapy of COVID-19-related ARDS.
33279332 Accumulating evidence supports the use of mesenchymal stem/stromal cells (MSCs), particularly bone marrow derived, as a safe and promising biologic therapy for promoting tissue repair and regeneration in various chronic diseases and disorders. […] Despite growing evidence that MSCs are potent anti-inflammatory mediators that can provide substantial benefits in acute organ injury, there are limited clinical trials utilizing MSCs in acute care settings, such as in the emergency department (ED) or intensive care unit (ICU). […] This article reviews the current state of MSC-based therapeutics and further explores the untapped potential role to treat various acute, life-threating injuries in the ED and ICU. […] All clinical trials using MSCs in acute myocardial infarction (AMI), acute respiratory distress syndrome (ARDS), sepsis and acute kidney injury (AKI) demonstrated safety. […] MSCs are potentially promising novel biologic therapeutics for clinical application in AMI, ARDS, sepsis, AKI and COVID-19 that have demonstrated safety in all clinical trials. […] More rigorous clinical trials are necessary and warranted to determine the efficacy of MSCs as a novel therapeutic in an acute setting, such as the ED.
33304473 The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID-19 patients. […] Instead, it is recommended to treat alternatively with their MSC-released exosomes. […] This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. […] Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. […] Additionally, in the context of COVID-19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID-19 disease process, causing significant central or peripheral vascular insufficiency.
33363221 In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. […] In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. […] We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.
33371042 Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. […] This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19.
33397585 This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. […] MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. […] The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. […] Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. […] Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. […] MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.
33400390 UC-MSCs; controls received two infusions of vehicle solution. […] No serious adverse events (SAEs) were observed related to UC-MSC infusions. […] UC-MSC infusions in COVID-19 ARDS were found to be safe. […] Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. […] UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS.
33407777 To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. […] To evaluate the effects of MSC on the secondary efficacy endpoints. […] To evaluate the safety and tolerability profiles of MSC. […] A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). […] Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects’ clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines…) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC.
33414832 Mesenchymal stem cells (MSCs), defined as plastic adherent cells with multipotent differentiation capacity in vitro, are an emerging and valuable tool to treat a plethora of diseases due to their therapeutic mechanisms such as their paracrine activity, mitochondrial and organelle transfer, and transfer of therapeutic molecules via exosomes. […] Nowadays, there are more than a thousand registered clinical trials related to MSC application around the world, highlighting MSC role on difficult-to-treat high-incidence diseases such as the current COVID-19, HIV infections, and autoimmune and metabolic diseases. […] Here, we summarize a general overview of MSCs and their therapeutic mechanisms; also, we discuss some of the novel clinical trial protocols and their results as well as a comparison between the number of registries, countries, and search portals.
33468250 Mesenchymal stem cells (MSCs) have been suggested as a potential treatment for ARDS due to their significant immunomodulatory properties. […] MSC small extracellular vesicles (sEVs), including exosomes, modulate the immune response as effectively as MSCs themselves, with the added advantages of increased safety and tissue penetration. […] We isolated sEVs from MSCs induced to secrete increased levels of neurotrophic and immunomodulatory factors, termed Exo MSC-NTF, and compared their ability to treat ARDS, in a lung injury LPS mouse model, to sEVs isolated from naïve MSCs (Exo MSC). […] We found that Exo MSC-NTF was superior to Exo MSC in reducing LPS-induced ARDS markers, including physiological lung damage such as alveolar wall thickness, fibrin presence, and neutrophil accumulation, as well as increasing oxygenation levels. […] Furthermore, Exo MSC-NTF reversed the imbalance in the host immune response, seen as decreased IFN-γ, IL-6, TNF-α, and RANTES levels in the bronchoalveolar lavage fluid. […] These positive preclinical results suggest that Exo MSC-NTF may be suitable as a therapy for COVID-19-induced ARDS and are more effective at combatting ARDS physiological, pathological, and biochemical symptoms than sEVs isolated from non-induced MSCs.
33511519 Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have emerged as a therapeutic option due to its intrinsic properties to alleviate inflammatory responses, capable to promote the restoring of injured tissue. […] This study investigated whether the MSC-EVs miRNA cargo has the capacity to modulate the exacerbated cytokines, cell death and coagulation disturbs present in severe COVID-19. […] Therefore, the MSC-derived EVs due to their heterogeneous cargo are a potential multitarget approach able to improve the survival rates of severe COVID-19 patients.
33514427 There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. […] In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). […] Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. […] We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. […] Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.
33522937 The success of the Sustainable Development Goals (SDGs) is predicated on multisectoral collaboration (MSC), and the COVID-19 pandemic makes it more urgent to learn how this can be done better. […] While the necessity of MSC is recognized, research is needed to understand how sectors collaborate, inform how to do so more efficiently, effectively and equitably, and ascertain similarities and differences across contexts. […] To answer these questions and inform practice, research to strengthen the evidence-base on MSC is critical. […] This paper draws on a 12-country study series on MSC for health and sustainable development, in the context of the health and rights of women, children and adolescents. […] We identify four considerations that are unique to MSC research which will be of interest to other researchers, in the context of COVID-19 and beyond: 1) use theoretical frameworks to frame research questions as relevant to all sectors and to facilitate theoretical generalizability and evolution; 2) specifically incorporate sectoral analysis into MSC research methods; 3) develop a core set of research questions, using mixed methods and contextual adaptations as needed, with agreement on criteria for research rigor; and 4) identify shared indicators of success and failure across sectors to assess MSCs. […] In responding to COVID-19 it is evident that effective MSC is an urgent priority.
33527780 Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. […] In this system, MSCs are seeded on the exterior of a hollow-fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore-size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. […] The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected “free” MSCs, a model of systemic administration. […] Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with “free” MSCs. […] Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time.
33551714 Mesenchymal stem cells (MSCs), as one of the leading cell-based therapy, have provided a strong link between clinical investigation and basic research. […] MSCs have been successfully employed in treating graft versus host disease (GvHD), autoimmune disease, and several other diseases, particularly with high immune activity. […] Recently, MSCs have attracted attention to treating untreatable viral infections such as severe coronavirus disease 2019 (COVID-19). […] Given that the Toll-like receptors (TLRs) are directly able to detect internal and external hazard signals, and their stimulation has an intense effect on the ability to grow, differentiate, migrate, and maintain MSCs, it seems stimulation of these receptors can have a direct impact on the interaction of MSCs and immune cells, altering the ability to modify immune system responses. […] Hence, this mini-review focused on TLRs’ critical roles in the polarization of MSCs for developing MSC-based therapy in viral infections. […] Consequently, according to the literature review, a polarization process, mediated by TLRs concerning anti-inflammatory and proinflammatory phenotype, may be considered for MSC-therapy against viral infections.
33562240 Compared to other applications, there has been little interest in the evaluation of mesenchymal stem cells (MSCs) and MSC-derived products (mostly extracellular vesicles) for the treatment of respiratory diseases. […] Due to the lack of efficient treatments for acute respiratory distress syndrome caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the action of MSCs has also been studied. […] This review describes mode of action and use of MSCs and MSC-derived products in the treatment of lung diseases including the respective advantages and limitations of the products. […] Administration by inhalation of MSCs, compared to intravenous injection, could decrease cell damage by shear stress, eliminate the barrier to reach target cells in the alveoli, prevent thrombus formation in the pulmonary vasculature and retention in filter for extracorporeal membrane oxygenation. […] There is more feasible to deliver extracellular vesicles than MSCs with inhalers, offering the advantage of non-invasive and repeated administration by the patient.
33579329 Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. […] However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. […] This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. […] Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. […] Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.
33580031 Mesenchymal stem cells (MSCs), multipotent stromal cells that mediate immunomodulation and regeneration, could be of potential benefit to a subset of COVID-19 subjects with acute respiratory failure. […] In this review, we discuss key features of the current COVID-19 outbreak, and the rationale for MSC-based therapy in this setting, as well as the limitations associated with this therapeutic approach.
33586320 Mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory abilities, have the potential to attenuate the cytokine storm and have therefore been proposed as a potential therapeutic approach for which several clinical trials are underway. […] Given that intravenous infusion of MSCs results in a significant trapping in the lung, MSC therapy could directly mitigate inflammation, protect alveolar epithelial cells, and reverse lung dysfunction by normalizing the pulmonary microenvironment and preventing pulmonary fibrosis. […] In this review, we present an overview and perspectives of the SARS-CoV-2 induced inflammatory dysfunction and the potential of MSC immunomodulation for the prevention and treatment of COVID-19 related pulmonary disease.