Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 65
Filter
Add filters

Document Type
Year range
1.
Front Biosci (Landmark Ed) ; 26(10): 948-961, 2021 10 30.
Article in English | MEDLINE | ID: covidwho-1498509

ABSTRACT

Background: Corona Virus Disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary pathogenesis is over-activation of the immune system. SARS-CoV-2 continues to mutate and spread rapidly and no effective treatment options are yet available. Mesenchymal stem cells (MSCs) are known to induce anti-inflammatory macrophages, regulatory T cells and dendritic cells. There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. Objective: To summarize the pathogenic mechanism of SARS-CoV-2, and systematically formulated the immunomodulation of COVID-19 by MSCs and their exosomes, as well as research progress. Method: Searching PubMed, clinicaltrials.gov and Chictr.cn for eligible studies to be published or registered by May 2021. Main keywords and search strategies were as follows: ((Mesenchymal stem cells) OR (MSCs)) AND (COVID-19). Results: MSCs regulate the immune system to prevent cytokine release syndrome (CRS) and to promote endogenous repair by releasing various paracrine factors and exosomes. Conclusions: MSC therapy is thus a promising candidate for COVID-19.


Subject(s)
COVID-19/therapy , Exosomes/transplantation , Immunomodulation/immunology , Lung Injury/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , COVID-19/epidemiology , COVID-19/virology , Clinical Trials as Topic , Exosomes/immunology , Exosomes/metabolism , Humans , Lung Injury/physiopathology , Lung Injury/virology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pandemics , Regeneration/immunology , Regeneration/physiology , SARS-CoV-2/immunology , SARS-CoV-2/physiology
2.
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
3.
Front Immunol ; 12: 738697, 2021.
Article in English | MEDLINE | ID: covidwho-1477824

ABSTRACT

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.


Subject(s)
COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/therapy , Mesenchymal Stem Cell Transplantation/methods , Cytokine Release Syndrome/pathology , Humans , Inflammation/therapy , Mesenchymal Stem Cells/immunology , SARS-CoV-2 , Sepsis/therapy
4.
Cells ; 10(10)2021 09 29.
Article in English | MEDLINE | ID: covidwho-1444117

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.


Subject(s)
COVID-19/blood , COVID-19/therapy , Lung/physiology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Regeneration/physiology , Animals , COVID-19/drug therapy , Cell Differentiation , Cell- and Tissue-Based Therapy , Culture Media , Extracellular Vesicles , Humans , Inflammation , Mice , Mice, SCID , Phenotype , Pneumonia/blood , Pneumonia/immunology , Pneumonia/therapy , Respiratory Distress Syndrome , SARS-CoV-2 , Thromboembolism/blood , Thromboembolism/immunology , Thromboembolism/therapy
5.
Curr Stem Cell Res Ther ; 16(4): 406-413, 2021.
Article in English | MEDLINE | ID: covidwho-1435705

ABSTRACT

COVID-19 pandemic is a global health crisis of the 21st Century. There are currently no approved vaccines and no particular anti-viral treatment for coronavirus disease. As COVID-19 has a broad range of illnesses, it is necessary to find a safe and effective therapeutic method for COVID-19. An attractive approach for treating COVID-19 is cell therapy. Cell therapy aims to inject new and healthy stem cells into a patient's body, to repair the damaged cells and tissues. Stem cell therapy is one of the most studied and important approaches in the treatment of COVID-19 these days. The significant clinical outcome was observed by the adoptive transfer of stem cells, specifically mesenchymal stem cells. This study reviews the characteristics of stem cells and clinical trials that have used stem cells in treating COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , Cell- and Tissue-Based Therapy , Mesenchymal Stem Cells/immunology , SARS-CoV-2/pathogenicity , COVID-19/virology , Cell- and Tissue-Based Therapy/methods , Humans , Mesenchymal Stem Cell Transplantation/methods
6.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1341694

ABSTRACT

The current coronavirus disease-19 (COVID-19) pandemic has strongly revived the pressing need to incorporate new therapeutic alternatives to deal with medical situations that result in a dramatic breakdown in the body's normal homeostasis [...].


Subject(s)
Acute Disease/therapy , COVID-19/therapy , Emergency Treatment/methods , Mesenchymal Stem Cell Transplantation/methods , Regenerative Medicine/methods , Acute Disease/mortality , COVID-19/mortality , Clinical Trials as Topic , Emergency Service, Hospital , Emergency Treatment/trends , Humans , Mesenchymal Stem Cell Transplantation/trends , Regenerative Medicine/trends , Survival Rate , Treatment Outcome
7.
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
8.
Eur Rev Med Pharmacol Sci ; 25(12): 4435-4438, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1296356

ABSTRACT

OBJECTIVE: We aimed at explaining the mechanism of therapeutic effect of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in subjects with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Patients with COVID-19 ARDS present with a hyperinflammatory response characterized by high levels of circulating pro-inflammatory mediators, including tumor necrosis factor α and ß (TNFα and TNFß). Inflammatory functions of these TNFs can be inhibited by soluble TNF Receptor 2 (sTNFR2). In patients with COVID-19 ARDS, UC-MSC appear to impart a robust anti-inflammatory effect, and treatment is associated with remarkable clinical improvements. We investigated the levels of TNFα, TNFß and sTNFR2 in blood plasma samples collected from subjects with COVID-19 ARDS enrolled in our trial of UC-MSC treatment. PATIENTS AND METHODS: We analyzed plasma samples from subjects with COVID-19 ARDS (n=24) enrolled in a Phase 1/2a randomized controlled trial of UC-MSC treatment. Plasma samples were obtained at Day 0 (baseline, before UC-MSC or control infusion), and Day 6 post infusion. Plasma concentrations of sTNFR2, TNFα, and TNFß were evaluated using a quantitative multiplex protein array. RESULTS: Our data indicate that at Day 6 after infusion, UC-MSC recipients develop significantly increased levels of plasma sTNFR2 and significantly decreased levels of TNFα and TNFß, compared to controls. CONCLUSIONS: These observations suggest that sTNFR2 plays a mechanistic role in mediating UC-MSC effect on TNFα and TNFß plasma levels, determining a decrease in inflammation in COVID-19 ARDS.


Subject(s)
COVID-19/blood , Lymphotoxin-alpha/blood , Mesenchymal Stem Cell Transplantation/methods , Receptors, Tumor Necrosis Factor, Type II/blood , Respiratory Distress Syndrome/blood , Tumor Necrosis Factor-alpha/blood , Umbilical Cord/transplantation , Biomarkers/blood , COVID-19/therapy , Double-Blind Method , Humans , Respiratory Distress Syndrome/therapy , Umbilical Cord/cytology
9.
Front Immunol ; 12: 659621, 2021.
Article in English | MEDLINE | ID: covidwho-1285289

ABSTRACT

Methods for suppressing the host immune system over the long term and improving transplantation tolerance remain a primary issue in organ transplantation. Cell therapy is an emerging therapeutic strategy for immunomodulation after transplantation. Mesenchymal stem cells (MSCs) are adult multipotent stem cells with wide differentiation potential and immunosuppressive properties, which are mostly used in regenerative medicine and immunomodulation. In addition, emerging research suggests that MSC-derived exosomes have the same therapeutic effects as MSCs in many diseases, while avoiding many of the risks associated with cell transplantation. Their unique immunomodulatory properties are particularly important in the immune system-overactive graft environment. In this paper, we review the effects of MSC-derived exosomes in the immune regulation mechanism after organ transplantation and graft-versus-host disease (GvHD) from various perspectives, including immunosuppression, influencing factors, anti-inflammatory properties, mediation of tissue repair and regeneration, and the induction of immune tolerance. At present, the great potential of MSC-derived exosomes in immunotherapy has attracted a great deal of attention. Furthermore, we discuss the latest insights on MSC-derived exosomes in organ transplantation and GvHD, especially its commercial production concepts, which aim to provide new strategies for improving the prognosis of organ transplantation patients.


Subject(s)
Exosomes/immunology , Immunomodulation/immunology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Organ Transplantation/methods , Transplantation Tolerance/immunology , Adult , Exosomes/metabolism , Graft vs Host Disease/immunology , Humans , Mesenchymal Stem Cells/metabolism , Regenerative Medicine/methods
10.
Stem Cells Transl Med ; 10(9): 1288-1303, 2021 09.
Article in English | MEDLINE | ID: covidwho-1233233

ABSTRACT

Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence. This has led to further expansion in clinical indications from graft rejection, autoimmune diseases, and osteoarthritis, to inflammatory liver and pulmonary diseases including COVID-19. A clear trend is the shift from using autologous to allogeneic MSCs, which can be immediately available as off-the-shelf products. In addition, new products such as cell-free exosomes and human pluripotent stem cell (hPSC)-derived MSCs are exciting developments to further prevalent use. Increasing numbers of trials have now published results in which safety of MSCT has been largely demonstrated. While reports of therapeutic endpoints are still emerging, efficacy can be seen for specific indications-including graft-vs-host-disease, strongly Th17-mediated autoimmune diseases, and osteoarthritis-which are more robustly supported by mechanistic preclinical evidence. In this review, we update and discuss outcomes in current MSCT clinical trials for immune and inflammatory disease, as well as new innovation and emerging trends in the field.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , SARS-CoV-2/drug effects , Graft vs Host Disease/therapy , Humans , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Pluripotent Stem Cells/classification
11.
Regen Med ; 16(5): 477-494, 2021 05.
Article in English | MEDLINE | ID: covidwho-1229139

ABSTRACT

In many countries, COVID-19 now accounts for more deaths per year than car accidents and even the deadliest wars. Combating the viral pandemics requires a coordinated effort to develop therapeutic protocols adaptable to the disease severity. In this review article, we summarize a graded approach aiming to shield cells from SARS-CoV-2 entry and infection, inhibit excess inflammation and evasion of the immune response, and ultimately prevent systemic organ failure. Moreover, we focus on mesenchymal stem cell therapy, which has shown safety and efficacy as a treatment of inflammatory and immune diseases. The cell therapy approach is now repurposed in patients with severe COVID-19. Numerous trials of mesenchymal stem cell therapy are ongoing, especially in China and the USA. Leader companies in cell therapy have also started controlled trials utilizing their quality assessed cell products. Results are too premature to reach definitive conclusions.


Subject(s)
COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , SARS-CoV-2/isolation & purification , COVID-19/virology , Clinical Trials as Topic , Humans
12.
Int Immunopharmacol ; 97: 107694, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1209540

ABSTRACT

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients' immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.


Subject(s)
COVID-19/therapy , Extracellular Vesicles/immunology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Respiratory Distress Syndrome/therapy , Anti-Inflammatory Agents/immunology , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Humans , Respiratory Distress Syndrome/etiology
13.
Life Sci ; 278: 119510, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1185153

ABSTRACT

Currently, the world has been devastated by an unprecedented pandemic in this century. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), has been causing disorders, dysfunction and morphophysiological alterations in multiple organs as the disease evolves. There is a great scientific community effort to obtain a therapy capable of reaching the multiple affected organs in order to contribute for tissue repair and regeneration. In this regard, mesenchymal stem cells (MSCs) have emerged as potential candidates concerning the promotion of beneficial actions at different stages of COVID-19. MSCs are promising due to the observed therapeutic effects in respiratory preclinical models, as well as in cardiac, vascular, renal and nervous system models. Their immunomodulatory properties and secretion of paracrine mediators, such as cytokines, chemokines, growth factors and extracellular vesicles allow for long range tissue modulation and, particularly, blood-brain barrier crossing. This review focuses on SARS-CoV-2 impact to lungs, kidneys, heart, vasculature and central nervous system while discussing promising MSC's therapeutic mechanisms in each tissue. In addition, MSC's therapeutic effects in high-risk groups for COVID-19, such as obese, diabetic and hypertensive patients are also explored.


Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation/methods , Animals , COVID-19/immunology , COVID-19/pathology , Humans , Immunomodulation , Mesenchymal Stem Cells/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
14.
Cell Transplant ; 30: 963689721996217, 2021.
Article in English | MEDLINE | ID: covidwho-1181030

ABSTRACT

COVID-19 has spread worldwide, including the United States, United Kingdom, and Italy, along with its site of origin in China, since 2020. The virus was first found in the Wuhan seafood market at the end of 2019, with a controversial source. The clinical symptoms of COVID-19 include fever, cough, and respiratory tract inflammation, with some severe patients developing an acute and chronic lung injury, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). It has already claimed approximately 300 thousand human lives and the number is still on the rise; the only way to prevent the infection is to be safe till vaccines and reliable treatments develop. In previous studies, the use of mesenchymal stem cells (MSCs) in clinical trials had been proven to be effective in immune modulation and tissue repair promotion; however, their efficacy in treating COVID-19 remains underestimated. Here, we report the findings from past experiences of SARS and MSCs, and how SARS could also induce PF. Such studies may help to understand the rationale for the recent cell-based therapies for COVID-19.


Subject(s)
COVID-19/complications , Mesenchymal Stem Cell Transplantation , Pulmonary Fibrosis/etiology , Animals , COVID-19/blood , COVID-19/pathology , COVID-19/therapy , Coronavirus/isolation & purification , Humans , Mesenchymal Stem Cell Transplantation/methods , Pulmonary Fibrosis/blood , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/therapy , Renin-Angiotensin System , SARS-CoV-2/isolation & purification , Severe Acute Respiratory Syndrome/blood , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/therapy , Transforming Growth Factor beta/blood
15.
Eur Rev Med Pharmacol Sci ; 25(6): 2748-2751, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1173126

ABSTRACT

COVID-19 is an acute respiratory infectious disease caused by SARS-COV 2 (Severe Acute Respiratory Syndrome Coronavirus) that has become a global pandemic. COVID-19 mainly causes the respiratory complications of Acute Respiratory Distress Syndrome (ARDS), cytokine storm, and severe immune disruptions. The assays depict that though people recuperate from COVID-19, there are still symptoms that persists in the body causing discomfort, which is the consequence of the viral infection due to severe immune disruptions. Upon various difficulties of post COVID-19, the pulmonary fibrosis is the stumbling block in the lungs causing severe damage. In this review, we have shown the effectiveness and importance of the Hepatocyte Growth Factor (HGF) secreted by Mesenchymal Stem Cell (MSC) therapy on selective stoppage of the Transforming Growth Factor-Beta (TGF-ß) signalling pathway by causing immunomodulatory effects that ameliorate the pulmonary fibrosis through paracrine signalling. However, more pilot studies have to be carried out to determine the efficacy and outcomes of the re-emerging complication.


Subject(s)
COVID-19/epidemiology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Pulmonary Fibrosis/therapy , Pulmonary Fibrosis/virology , COVID-19/transmission , COVID-19/virology , Global Health , Humans , Pulmonary Fibrosis/epidemiology , SARS-CoV-2/isolation & purification
16.
J Cell Physiol ; 236(10): 7266-7289, 2021 10.
Article in English | MEDLINE | ID: covidwho-1168883

ABSTRACT

Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche-dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell-based therapy in tackling several pathological conditions including COVID-19. Iron is essential for MSC processes but iron-loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron-related proteins in MSC physiology. It describes the contribution of iron and endogenous iron-related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin-2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess-iron-induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron-toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron-excess, namely, hereditary hemochromatosis, diabetes, ß-thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron-perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron-linked MSC-contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron-based therapies for excess-iron conditions, and thereby inform regenerative medicine.


Subject(s)
Iron/metabolism , Mesenchymal Stem Cells/metabolism , Animals , Cell Differentiation/physiology , Cell- and Tissue-Based Therapy/methods , Humans , Immunomodulation/physiology , Mesenchymal Stem Cell Transplantation/methods , Regenerative Medicine/methods , Signal Transduction/physiology
17.
Front Immunol ; 11: 591065, 2020.
Article in English | MEDLINE | ID: covidwho-1146667

ABSTRACT

Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent stem cells derived from mesoderm, which can be easily isolated from many sources such as bone marrow, umbilical cord or adipose tissue. MSCs provide support for hematopoietic stem cells and have an ability to differentiate into multiple cell lines. Moreover, they have proangiogenic, protective and immunomodulatory properties. MSCs have the capacity to modulate both innate and adaptive immune responses, which accompany many diseases, by inhibiting pro-inflammatory reactions and stimulating anti-inflammatory activity. Recent findings revealed that the positive effect of MSCs is at least partly associated with the production of extracellular vesicles (EVs). EVs are small membrane structures, containing proteins, lipids and nuclei acids, which take part in intra-cellular communication. Many studies indicate that EVs contain protective and pro-regenerative properties and can modulate an immune response that is activated in various diseases such as CNS diseases, myocardial infarction, liver injury, lung diseases, ulcerative colitis or kidney injury. Thus, EVs have similar functions as their cells of origin and since they do not carry the risk of cell transplantation, such as tumor formation or small vessel blockage, they can be considered a potential therapeutic tool for cell-free therapy.


Subject(s)
Extracellular Vesicles/metabolism , Immunomodulation , Mesenchymal Stem Cells/metabolism , Animals , Biomarkers , Cell Communication/immunology , Cell- and Tissue-Based Therapy/methods , Clinical Trials as Topic , Disease Management , Humans , Immunity, Innate , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology
18.
Stem Cells Dev ; 30(9): 459-472, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1132412

ABSTRACT

Corona virus disease 2019 (COVID-19) refers to a type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Sixty million confirmed cases have been reported worldwide until November 29, 2020. Unfortunately, the novel coronavirus is extremely contagious and the mortality rate of severe and critically ill patients is high. Thus, there is no definite and effective treatment in clinical practice except for antiviral therapy and supportive therapy. Mesenchymal stem cells (MSCs) are not only characterized by low immunogenicity and homing but also have anti-inflammatory and immunomodulation characteristics. Furthermore, they can inhibit the occurrence and development of a cytokine storm, inhibit lung injury, and exert antipulmonary fibrosis and antioxidative stress, therefore MSC therapy is expected to become one of the effective therapies to treat severe COVID-19. This article will review the possible mechanisms of MSCs in the treatment of severe COVID-19.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/prevention & control , Lung Injury/prevention & control , Mesenchymal Stem Cell Transplantation/methods , Pulmonary Fibrosis/prevention & control , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Humans , Immunomodulation/immunology , Mesenchymal Stem Cells/cytology , Oxidative Stress , SARS-CoV-2/immunology
19.
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
20.
Curr Opin Pulm Med ; 27(3): 205-209, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1101916

ABSTRACT

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus-2-induced hyperinflammation is a major cause of death or end-organ dysfunction in COVID-19 patients. We review adjunct host-directed therapies (HDTs) for COVID-19 management. RECENT FINDINGS: The use of umbilical cord-derived mesenchymal stem cells as HDT for COVID-19 has been shown to be safe in phase 1 and 2 trials. Trials of anti-interleukin-6 receptor antibodies show promising mortality benefit in hospitalized COVID-19 patients. Repurposed drugs and monoclonal antibodies targeting specific cytokines acting on different aspects of the pro- and anti-inflammatory cascades are under evaluation. SUMMARY: A range of HDTs shows promise for reducing mortality and improving long term disability in patients with severe COVID-19, and require evaluation in randomized, controlled trials.


Subject(s)
COVID-19 , Immunologic Factors/pharmacology , Mesenchymal Stem Cell Transplantation/methods , Molecular Targeted Therapy/methods , COVID-19/immunology , COVID-19/therapy , Humans , Inflammation/immunology , Inflammation/therapy , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL
...