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1.
Hum Cell ; 35(6): 1633-1639, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2014580

ABSTRACT

Endothelial dysfunction is one of the key cornerstone complications of emerging and re-emerging viruses which lead to vascular leakage and a high mortality rate. The mechanism that regulates the origin of endothelial dysregulation is not completely elucidated. Currently, there are no potential pharmacological treatments and curable management for such diseases. In this sense, mesenchymal stromal/stem cells (MSCs) has been emerging to be a promising therapeutic strategy in restoring endothelial barrier function in various lung disease, including ALI and ARDS. The mechanism of the role of MSCs in restoring endothelial integrity among single-strand RNA (ssRNA) viruses that target endothelial cells remains elusive. Thus, we have discussed the therapeutic role of MSCs in restoring vascular integrity by (i) inhibiting the metalloprotease activity thereby preventing the cleavage of tight junction proteins, which are essential for maintaining membrane integrity (ii) possessing antioxidant properties which neutralize the excessive ROS production due to virus infection and its associated hyper host immune response (iii) modulating micro RNAs that regulate the endothelial activation and its integrity by downregulating the inflammatory response during ssRNA infection.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Virus Diseases , Antioxidants/metabolism , Endothelial Cells/metabolism , Humans , Mesenchymal Stem Cells/physiology , Metalloproteases/metabolism , RNA , Reactive Oxygen Species/metabolism , Tight Junction Proteins/metabolism , Virus Diseases/metabolism
2.
Int J Mol Sci ; 23(3)2022 Jan 24.
Article in English | MEDLINE | ID: covidwho-1650418

ABSTRACT

Acute Respiratory Distress Syndrome is the most common cause of respiratory failure among critically ill patients, and its importance has been heightened during the COVID-19 pandemic. Even with the best supportive care, the mortality rate in the most severe cases is 40-50%, and the only pharmacological agent shown to be of possible benefit has been steroids. Mesenchymal stromal cells (MSCs) have been tested in several pre-clinical models of lung injury and been found to have significant therapeutic benefit related to: (a) potent immunomodulation; (b) secretion of epithelial and endothelial growth factors; and (c) augmentation of host defense to infection. Initial translational efforts have shown signs of promise, but the results have not yielded the anticipated outcomes. One potential reason is the relatively low survival of MSCs in inflammatory conditions as shown in several studies. Therefore, strategies to boost the survival of MSCs are needed to enhance their therapeutic effect. Protease-activated receptors (PARs) may represent one such possibility as they are G-protein coupled receptors expressed by MSCs and control several facets of cell behavior. This review summarizes some of the existing literature about PARs and MSCs and presents possible future areas of investigation in order to develop potential, PAR-modified MSCs with enhanced therapeutic efficiency.


Subject(s)
Graft Survival/genetics , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Receptors, Proteinase-Activated/physiology , Respiratory Distress Syndrome/therapy , Animals , COVID-19/genetics , COVID-19/pathology , COVID-19/therapy , Cell Survival/genetics , Critical Illness/therapy , Humans , Mesenchymal Stem Cells/physiology , Receptors, Proteinase-Activated/genetics , Receptors, Proteinase-Activated/metabolism , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , SARS-CoV-2/physiology , Signal Transduction/physiology , Transfection , Treatment Outcome
3.
Stem Cells Transl Med ; 10(11): 1482-1490, 2021 11.
Article in English | MEDLINE | ID: covidwho-1490914

ABSTRACT

As our life expectancy increases, specific medical conditions appear, and new challenges are met in terms of global health. Frailty has become a medical and scientific concept to define pathologies where inflammation, depressed immune system, cellular senescence, and molecular aging converge. But more importantly, frailty is the ultimate cause of death that limits our life span and deteriorates health in an increasing proportion of the world population. The difficulty of tackling this problem is the combination of factors that influence frailty appearance, such as stem cells exhaustion, inflammation, loss of regeneration capability, and impaired immunomodulation. To date, multiple research fields have found mechanisms participating in this health condition, but to make progress, science will need to investigate frailty with an interdisciplinary approach. This article summarizes the current efforts to understand frailty from their processes mediated by inflammation, aging, and stem cells to provide a new perspective that unifies the efforts in producing advanced therapies against medical conditions in the context of frailty. We believe this approach against frailty is particularly relevant to COVID-19, since people in a state of frailty die more frequently due to the hyperinflammatory process associated with this infection.


Subject(s)
COVID-19 , Frailty , Inflammation/complications , Mesenchymal Stem Cell Transplantation , Aging/physiology , COVID-19/complications , COVID-19/therapy , Frailty/etiology , Frailty/therapy , Humans , Immunomodulation/physiology , Inflammation/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/physiology , Regeneration/physiology , SARS-CoV-2 , Signal Transduction/physiology
4.
Cells ; 10(8)2021 08 01.
Article in English | MEDLINE | ID: covidwho-1348603

ABSTRACT

Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.


Subject(s)
Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Regenerative Medicine , Animals , Exosomes/physiology , Humans , Mesenchymal Stem Cells/physiology , Tissue Engineering
5.
Int J Mol Sci ; 22(15)2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1335093

ABSTRACT

Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/therapy , Acute Lung Injury/complications , Acute Lung Injury/therapy , COVID-19/complications , COVID-19/therapy , Exosomes/transplantation , Humans , Mesenchymal Stem Cells/chemistry , Respiratory Distress Syndrome/etiology
6.
OMICS ; 25(6): 342-357, 2021 06.
Article in English | MEDLINE | ID: covidwho-1266096

ABSTRACT

Early cell biology reports demonstrated the presence of cells with stem-like properties in bone marrow, with both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multilineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and versatile potentials, MSCs are leveraged in many applications in medicine such as oncology, bioprinting, and as recent as therapeutics discovery and innovation for COVID-19. To date, studies indicate that MSCs have varied differentiation capabilities into different cell types, and demonstrate immunomodulating and anti-inflammatory properties. Different microenvironments or niche for MSCs and their resulting heterogeneity may influence attendant cellular behavior and differentiation capacity. The potential clinical applications of MSCs and exosomes derived from these cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. There is ample reason to think, as discussed in this expert review that the future looks bright and promising for MSC research, with many clinical trials under way to ascertain their clinical utility. This review provides a synthesis of the latest advances and trends in MSC research to allow for broad and critically informed use of MSCs. Early observations of the presence of these cells in the bone marrow and their remarkable differentiation capabilities and immunomodulation are also presented.


Subject(s)
Cell Differentiation , Immunomodulation , Mesenchymal Stem Cells/immunology , Humans , Mesenchymal Stem Cells/physiology , Regenerative Medicine , Stem Cell Niche , Tissue Engineering
7.
Stem Cells Dev ; 30(15): 758-772, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1254367

ABSTRACT

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.


Subject(s)
Cytokine Release Syndrome/prevention & control , Extracellular Vesicles/physiology , Mesenchymal Stem Cells/cytology , SARS-CoV-2/physiology , Wharton Jelly/cytology , Adult , Aged , COVID-19/blood , COVID-19/complications , COVID-19/metabolism , COVID-19/therapy , Cells, Cultured , Coculture Techniques , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/virology , Cytokines/genetics , Cytokines/metabolism , Diabetes Complications/blood , Diabetes Complications/metabolism , Diabetes Complications/therapy , Diabetes Complications/virology , Diabetes Mellitus/blood , Diabetes Mellitus/metabolism , Diabetes Mellitus/therapy , Diabetes Mellitus/virology , Dose-Response Relationship, Drug , Female , Gene Expression Regulation/drug effects , Glucose/metabolism , Glucose/pharmacology , Humans , Inflammation Mediators/metabolism , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Pregnancy , Toxins, Biological/metabolism , Toxins, Biological/pharmacology , Umbilical Cord/cytology , Uremia/blood , Uremia/complications , Uremia/metabolism , Uremia/therapy
8.
Int J Dev Biol ; 64(10-11-12): 465-469, 2020.
Article in English | MEDLINE | ID: covidwho-1159910

ABSTRACT

Mesenchymal stem cells (MSCs) are used as therapeutic agents for the treatment of a wide spectrum of diseases, as well as for the regeneration and healing of burns and wounds. MSCs have an immunomodulatory effect and influence the phenotype and functions of immune cells, including macrophages, which in turn prime and license the MSCs. We discuss the new findings on the feedback loop between MSCs and macrophages and its consequences on the outcome of MSC therapies.


Subject(s)
Macrophages/physiology , Mesenchymal Stem Cells/physiology , Cell Communication , Humans , Macrophages/immunology , Mesenchymal Stem Cell Transplantation
9.
Crit Care Med ; 48(5): e391-e399, 2020 05.
Article in English | MEDLINE | ID: covidwho-661181

ABSTRACT

OBJECTIVES: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. DESIGN: Prospective phase I clinical trial. SETTING: Medical center in Kaohsiung, Taiwan. PATIENTS: Moderate-to-severe acute respiratory distress syndrome with a PaO2/FIO2 ratio less than 200. INTERVENTIONS: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) and mesenchymal stem cell markers (CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell/Cytotoxity-T-cell/Regulatory-T-cell) were notably increased (p for trend < 0.001) after cell infusion. CONCLUSIONS: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/therapy , Umbilical Cord/physiology , Adult , Aged , Drug Dosage Calculations , Female , Hospital Mortality/trends , Humans , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/mortality , Mesenchymal Stem Cells/classification , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/mortality , Severity of Illness Index
10.
Cytokine Growth Factor Rev ; 58: 114-133, 2021 04.
Article in English | MEDLINE | ID: covidwho-1007960

ABSTRACT

The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. 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. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. 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. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , COVID-19/epidemiology , Cell- and Tissue-Based Therapy/methods , Cell- and Tissue-Based Therapy/trends , Humans , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Multiple Organ Failure/prevention & control , Multiple Organ Failure/therapy , SARS-CoV-2/pathogenicity
11.
J Transl Med ; 18(1): 451, 2020 11 30.
Article in English | MEDLINE | ID: covidwho-949113

ABSTRACT

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. METHODS: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. RESULTS: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes. CONCLUSIONS: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.


Subject(s)
COVID-19/therapy , Delivery of Health Care/organization & administration , Dry Ice , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Point-of-Care Systems/organization & administration , Transportation , Acute Disease , COVID-19/epidemiology , COVID-19/pathology , Cell Proliferation , Cell Survival , Cells, Cultured , Cord Blood Stem Cell Transplantation/adverse effects , Delivery of Health Care/standards , Equipment and Supplies, Hospital/standards , Equipment and Supplies, Hospital/supply & distribution , Graft vs Host Disease/etiology , Graft vs Host Disease/pathology , Graft vs Host Disease/therapy , Humans , Italy/epidemiology , Materials Management, Hospital/organization & administration , Materials Management, Hospital/standards , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/standards , Mesenchymal Stem Cells/physiology , Organization and Administration/standards , Pandemics , Phenotype , Point-of-Care Systems/standards , SARS-CoV-2/physiology , Severity of Illness Index , Transportation/methods , Transportation/standards
12.
Anal Cell Pathol (Amst) ; 2020: 1939768, 2020.
Article in English | MEDLINE | ID: covidwho-939923

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the development of a new coronavirus disease (COVID-19), is a highly transmittable virus which, in just ten months, infected more than 40 million people in 214 countries worldwide. After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS). Since there are no specific drugs or vaccines available to cure or prevent COVID-19 infection and COVID-19-related ARDS, a new therapeutic agent which will support oxygen supply and, at the same time, efficiently alleviate SARS-CoV-2-induced lung inflammation is urgently needed. 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.


Subject(s)
Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2/pathogenicity , COVID-19/therapy , COVID-19/virology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Humans , Pandemics
13.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Article in English | MEDLINE | ID: covidwho-631298

ABSTRACT

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.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Virus Diseases/therapy , Virus Physiological Phenomena , Animals , Betacoronavirus/physiology , COVID-19 , Cell Culture Techniques , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , HIV/physiology , Hepatitis B virus/physiology , Humans , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Diseases/epidemiology , Virus Diseases/immunology , Viruses/pathogenicity
14.
Protein Cell ; 11(10): 707-722, 2020 10.
Article in English | MEDLINE | ID: covidwho-626150

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. 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.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Mesenchymal Stem Cell Transplantation , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/therapy , Adoptive Transfer , Alveolar Epithelial Cells/pathology , Animals , Apoptosis , Body Fluids/metabolism , CD4-Positive T-Lymphocytes/immunology , COVID-19 , Clinical Trials as Topic , Coinfection/prevention & control , Coinfection/therapy , Coronavirus Infections/immunology , Disease Models, Animal , Endothelial Cells/pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Genetic Vectors/therapeutic use , Humans , Immunity, Innate , Inflammation Mediators/metabolism , Lung/pathology , Lung/physiopathology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , SARS-CoV-2
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