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1.
Front Immunol ; 13: 963445, 2022.
Article in English | MEDLINE | ID: covidwho-2141996

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. It may occur during the pancytopenia phase following allogeneic hematopoietic cell transplantation (HCT). ARDS is rare following HCT. Mesenchymal stromal cells (MSCs) have strong anti-inflammatory effect and first home to the lung following intravenous infusion. MSCs are safe to infuse and have almost no side effects. During the Covid-19 pandemic many patients died from ARDS. Subsequently MSCs were evaluated as a therapy for Covid-19 induced ARDS. We report three patients, who were treated with MSCs for ARDS following HCT. Two were treated with MSCs derived from the bone marrow (BM). The third patient was treated with MSCs obtained from the placenta, so-called decidua stromal cells (DSCs). In the first patient, the pulmonary infiltrates cleared after infusion of BM-MSCs, but he died from multiorgan failure. The second patient treated with BM-MSCs died of aspergillus infection. The patient treated with DSCs had a dramatic response and survived. He is alive after 7 years with a Karnofsky score of 100%. We also reviewed experimental and clinical studies using MSCs or DSCs for ARDS. Several positive reports are using MSCs for sepsis and ARDS in experimental animals. In man, two prospective randomized placebo-controlled studies used adipose and BM-MSCs, respectively. No difference in outcome was seen compared to placebo. Some pilot studies used MSCs for Covid-19 ARDS. Positive results were achieved using umbilical cord and DSCs however, optimal source of MSCs remains to be elucidated using randomized trials.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Male , Animals , Female , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/methods , COVID-19/therapy , Prospective Studies , Pandemics , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Hematopoietic Stem Cell Transplantation/adverse effects
2.
Curr Pharm Des ; 28(36): 2991-2994, 2022.
Article in English | MEDLINE | ID: covidwho-2054718

ABSTRACT

COVID-19, which has strongly affected the 21st century, is caused by severe acute respiratory syndrome (SARS)-CoV-2. The emergence of viral variants has rendered even vaccinated people prone to infection; thus, completely eradicating COVID-19 may be impossible. COVID-19 causes hyperinflammation, leading to organ damage and even death. SARS-CoV-2 infects not only the lungs, causing acute respiratory distress syndrome, but also the extrapulmonary organs. Not all patients with COVID-19 respond adequately to treatments with antiviral and anti-inflammatory drugs. Therefore, new treatments are urgently needed. Mesenchymal stem cells (MSCs) exhibit immunomodulatory activity and are used to safely and effectively treat various immune disorders. Evidence has indicated the efficacy of MSCs against COVID-19. However, the safety and efficacy of MSCs must be probed further. For this reason, we explored key clinical challenges associated with MSC therapy for COVID-19, such as sources, administration routes, cell dosage, treatment timepoint, and virus reactivation. We identified several challenges that must be addressed before MSCs can be clinically applied.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Humans , COVID-19/therapy , SARS-CoV-2
3.
Stem Cells Transl Med ; 11(11): 1103-1112, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2051544

ABSTRACT

Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Male , Humans , Aged, 80 and over , SARS-CoV-2 , Cytokine Release Syndrome , Mesenchymal Stem Cell Transplantation/methods , Respiratory Distress Syndrome/therapy , Cytokines
4.
Stem Cell Res Ther ; 13(1): 365, 2022 07 28.
Article in English | MEDLINE | ID: covidwho-2021331

ABSTRACT

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , COVID-19/therapy , Humans , Iran , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/methods , Pandemics , Respiratory Distress Syndrome/therapy , SARS-CoV-2
6.
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
7.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2010107

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated. The secretome of MSCs consists of cytokines, chemokines, signaling molecules, and growth factors, which effectively contribute to the regulation of immune and inflammatory responses. The immunomodulatory effects of MSCs can also be achieved through direct cell contact with microenvironmental factors and immune cells. Furthermore, preconditioned and engineered MSCs can specifically improve the immunomodulation effects in diverse clinical applications. These multifunctional properties of MSCs enable them to be used as a prospective therapeutic strategy to treat immune disorders, including autoimmune diseases and incurable inflammatory diseases. Here we review the recent exploration of immunomodulatory mechanisms of MSCs and briefly discuss the promotion of the genetically engineered MSCs. Additionally, we review the potential clinical applications of MSC-mediated immunomodulation in four types of immune diseases, including systemic lupus erythematosus, Crohn's disease, graft-versus-host disease, and COVID-19.


Subject(s)
COVID-19 , Immune System Diseases , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Cytokines/metabolism , Humans , Immune System Diseases/metabolism , Immunity , Immunomodulation , Mesenchymal Stem Cells/metabolism
8.
Cells ; 11(17)2022 08 29.
Article in English | MEDLINE | ID: covidwho-2005945

ABSTRACT

Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Cytokine Release Syndrome/therapy , Cytokines/metabolism , Humans , Mesenchymal Stem Cells/metabolism
9.
Front Immunol ; 13: 932360, 2022.
Article in English | MEDLINE | ID: covidwho-2002493

ABSTRACT

Background: Treatment of acute respiratory distress syndrome (ARDS) associated with COronaVIrus Disease-2019 (COVID-19) currently relies on dexamethasone and supportive mechanical ventilation, and remains associated with high mortality. Given their ability to limit inflammation, induce immune cells into a regulatory phenotype and stimulate tissue repair, mesenchymal stromal cells (MSCs) represent a promising therapy for severe and critical COVID-19 disease, which is associated with an uncontrolled immune-mediated inflammatory response. Methods: In this phase I-II trial, we aimed to evaluate the safety and efficacy of 3 intravenous infusions of bone marrow (BM)-derived MSCs at 3-day intervals in patients with severe COVID-19. All patients also received dexamethasone and standard supportive therapy. Between June 2020 and September 2021, 8 intensive care unit patients requiring supplemental oxygen (high-flow nasal oxygen in 7 patients, invasive mechanical ventilation in 1 patient) were treated with BM-MSCs. We retrospectively compared the outcomes of these MSC-treated patients with those of 24 matched control patients. Groups were compared by paired statistical tests. Results: MSC infusions were well tolerated, and no adverse effect related to MSC infusions were reported (one patient had an ischemic stroke related to aortic endocarditis). Overall, 3 patients required invasive mechanical ventilation, including one who required extracorporeal membrane oxygenation, but all patients ultimately had a favorable outcome. Survival was significantly higher in the MSC group, both at 28 and 60 days (100% vs 79.2%, p = 0.025 and 100% vs 70.8%, p = 0.0082, respectively), while no significant difference was observed in the need for mechanical ventilation nor in the number of invasive ventilation-free days, high flow nasal oxygenation-free days, oxygen support-free days and ICU-free days. MSC-treated patients also had a significantly lower day-7 D-dimer value compared to control patients (median 821.0 µg/L [IQR 362.0-1305.0] vs 3553 µg/L [IQR 1155.0-6433.5], p = 0.0085). Conclusions: BM-MSC therapy is safe and shows very promising efficacy in severe COVID-19, with a higher survival in our MSC cohort compared to matched control patients. These observations need to be confirmed in a randomized controlled trial designed to demonstrate the efficacy of BM-MSCs in COVID-19 ARDS. Clinical Trial Registration: (www.ClinicalTrials.gov), identifier NCT04445454.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Bone Marrow , COVID-19/therapy , Dexamethasone , Humans , Oxygen , Respiratory Distress Syndrome/therapy , Retrospective Studies , SARS-CoV-2
10.
Stem Cell Res Ther ; 13(1): 410, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-1993380

ABSTRACT

Since December 2019, the coronavirus (COVID-19) pandemic has imposed huge burdens to the whole world, seriously affecting global economic growth, and threatening people's lives and health. At present, some therapeutic regimens are available for treatment of COVID-19 pneumonia, including antiviral therapy, immunity therapy, anticoagulant therapy, and others. Among them, injection of mesenchymal stem cells (MSCs) is currently a promising therapy. The preclinical studies and clinical trials using MSCs and small extracellular vesicles derived from MSCs (MSC-sEVs) in treating COVID-19 were summarized. Then, the molecular mechanism, feasibility, and safety of treating COVID-19 with MSCs and MSC-sEVs were also discussed.


Subject(s)
COVID-19 , Coronavirus Infections , Extracellular Vesicles , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/drug therapy , COVID-19/therapy , Coronavirus Infections/therapy , Humans
11.
Cells ; 11(15)2022 07 27.
Article in English | MEDLINE | ID: covidwho-1969102

ABSTRACT

Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal stem cell (MSC) therapy offers a new approach with minimal side effects. MSCs and MSC-based products possess several biological properties that potentially alleviate COVID-19 symptoms. Generally, there are three classifications of stem cell therapy: cell-based therapy, tissue engineering, and cell-free therapy. This review discusses the MSC-based and cell-free therapies for patients with COVID-19, their potential mechanisms of action, and clinical trials related to these therapies. Cell-based therapies involve the direct use and injection of MSCs into the target tissue or organ. On the other hand, cell-free therapy uses secreted products from cells as the primary material. Cell-free therapy materials can comprise cell secretomes and extracellular vesicles. Each therapeutic approach possesses different benefits and various risks. A better understanding of MSC-based and cell-free therapies is essential for supporting the development of safe and effective COVID-19 therapy.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Cell- and Tissue-Based Therapy , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , SARS-CoV-2
12.
DNA Cell Biol ; 41(8): 768-777, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1967830

ABSTRACT

At present, severe acute respiratory syndrome coronavirus 2 is spreading and has caused over 188 million confirmed patients and more than 4,059,101 deaths. Currently, several clinical trials are done using mesenchymal stem cell (MSC) therapy in patients with coronavirus disease 2019 (COVID-19). These cells have shown safety and effectiveness, implying a promising clinical application in patients with COVID-19. Studies have shown that abnormalities in hematological measures such as white blood cells count, neutrophilia, elevated neutrophil to lymphocyte ratio, inflammatory markers, and lactate dehydrogenase can be used to assess the severity of COVID-19 disease and the response to therapy following MSC treatment. Our study has aimed to review the role of hematological factors in determination of responsiveness to MSC therapy and disease severity in COVID-19 patients.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Humans , SARS-CoV-2
13.
Stem Cell Res Ther ; 13(1): 257, 2022 06 17.
Article in English | MEDLINE | ID: covidwho-1962893

ABSTRACT

The SARS-COV-2 virus has infected the world at a very high rate by causing COVID-19 disease. Nearly 507 million individuals have been infected with this virus, with approximately 1.2% of these patients being dead, indicating that this virus has been out of control in many countries. While researchers are investigating how to develop efficient drugs and vaccines versus the COVID-19 pandemic, new superseded treatments have the potential to reduce mortality. The recent application of mesenchymal stem cells (MSCs) in a subgroup of COVID-19 patients with acute respiratory distress has created potential benefits as supportive therapy for this viral contagion in patients with acute conditions and aged patients with severe pneumonia. Consequently, within this overview, we discuss the role and therapeutic potential of MSCs and the challenges ahead in using them to treat viral infections, with highlighting on COVID-19 infection.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Aged , COVID-19/therapy , Humans , Pandemics , SARS-CoV-2
14.
Int J Mol Sci ; 23(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957348

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Acute Lung Injury/etiology , Acute Lung Injury/therapy , Animals , COVID-19/therapy , Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Models, Animal , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2
15.
Immunotherapy ; 14(13): 1055-1065, 2022 09.
Article in English | MEDLINE | ID: covidwho-1952097

ABSTRACT

The human immune system protects the body against invasive organisms and kicks into a hyperactive mode in COVID-19 patients, particularly in those who are critically sick. Therapeutic regimens directed at the hyperactive immune system have been found to be effective in the treatment of patients with COVID-19. An evolving potential treatment option is therapy with mesenchymal stem cells (MSCs) due to their regenerative and reparative ability in epithelial cells. Clinical trials have reported the safe usage of MSC therapy. Systemic effects of MSC treatment have included a reduction in pro-inflammatory cytokines and a decrease in the levels of CRP, IL-6, and lactase dehydrogenase, which function as independent biomarkers for COVID-19 mortality and respiratory failure.


Treatment of COVID-19 is becoming increasingly difficult because of new variants, such as Delta, and more recently Omicron. Each virus variant becomes smarter at being able to evade the body's immune system, vaccines and drug treatments. The biggest challenge in treating COVID-19 is when the body's immune system starts to become hyperactive. In such a scenario, the immune system releases the compounds that are supposed to be released in small doses all at once. Thus, overwhelming the body and causing many complications. One possible solution to this is the mesenchymal stem cell. Multiple clinical trials have shown that mesenchymal stem cells can heal all different cell types in the body and stop the hyperactive immune system.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Humans , Immunity , Mesenchymal Stem Cell Transplantation/adverse effects , SARS-CoV-2
16.
Stem Cell Res Ther ; 13(1): 321, 2022 07 16.
Article in English | MEDLINE | ID: covidwho-1938350

ABSTRACT

BACKGROUND: The novel coronavirus is still mutating, and the pandemic continues. Meanwhile, many COVID-19 survivors have residual postinfection clinical manifestations. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been shown to be effective in the early stages of COVID-19. OBJECTIVES: The aim of this study was to investigate long-term safety and efficacy of treatment in patients with severe COVID-19 patients who had received hUC-MSCs therapy. METHODS: Twenty-five discharged patients who had severe COVID-19 (including the standard treatment group and the standard treatment plus hUC-MSCs group) were enrolled in a 1-year follow-up. The assessment considered adverse effects (including effects on liver and kidney function, coagulation, ECG, tumor marker, and so on), pulmonary function, St George's Respiratory Questionnaire (SGRQ), postinfection sequelae and serum concentration of Krebs von den Lungen-6 (KL-6), malondialdehyde (MDA), H2S, carnitine, and N-6 long-chain polyunsaturated fatty acids (N-6 LC-PUFAs). MEASUREMENTS AND MAIN RESULTS: Pulmonary ventilation function had significantly improved at the 1-year follow-up in both the hUC-MSCs group and the control group compared with the 3-month follow-up (P < 0.01). Fatigue (60% [15/25]) remained the most common symptom at the 1-year follow-up. The rate of fatigue relief was significantly reduced in the hUC-MSCs group (25% [2/8]) compared to the control group (76.5% [13/17]) (P = 0.028). The level of KL-6 was significantly lower in the hUC-MSCs group (2585.5 ± 186.5 U/ml) than in the control group (3120.7 ± 158.3 U/ml) (P < 0.001). Compared with the control group, the hUC-MSCs group had a lower level of MDA (9.27 ± 0.54 vs. 9.91 ± 0.72 nmol/ml, P = 0.036). No obvious adverse effects were observed in the hUC-MSCs treatment group at 1 year after discharge. CONCLUSIONS: Intravenous transplantation of hUC-MSCs was a safe approach in the long term in the treatment of patients with severe COVID-19. In addition, hUC-MSCs had a positive effect on postinfection sequelae in COVID-19 survivors. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020-Retrospectively registered, http://www.medresman.org.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Fatigue , Follow-Up Studies , Humans , Umbilical Cord
17.
Pharmacol Res ; 182: 106334, 2022 08.
Article in English | MEDLINE | ID: covidwho-1914898

ABSTRACT

Coronavirus disease 2019 (COVID-19) infection evokes severe proinflammatory storm and pulmonary infection with the number of confirmed cases (more than 200 million) and mortality (5 million) continue to surge globally. A number of vaccines (e.g., Moderna, Pfizer, Johnson/Janssen and AstraZeneca vaccines) have been developed over the past two years to restrain the rapid spread of COVID-19. However, without much of effective drug therapies, COVID-19 continues to cause multiple irreversible organ injuries and is drawing intensive attention for cell therapy in the management of organ damage in this devastating COVID-19 pandemic. For example, mesenchymal stem cells (MSCs) have exhibited promising results in COVID-19 patients. Preclinical and clinical findings have favored the utility of stem cells in the management of COVID-19-induced adverse outcomes via inhibition of cytokine storm and hyperinflammatory syndrome with coinstantaneous tissue regeneration capacity. In this review, we will discuss the existing data with regards to application of stem cells for COVID-19.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Cell- and Tissue-Based Therapy , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Pandemics
18.
Cytotherapy ; 24(8): 755-766, 2022 08.
Article in English | MEDLINE | ID: covidwho-1914577

ABSTRACT

Currently, treating coronavirus disease 2019 (COVID-19) patients, particularly those afflicted with severe pneumonia, is challenging, as no effective pharmacotherapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Severe pneumonia is recognized as a clinical syndrome characterized by hyper-induction of pro-inflammatory cytokine production, which can induce organ damage, followed by edema, dysfunction of air exchange, acute respiratory distress syndrome, acute cardiac injury, secondary infection and increased mortality. Owing to the immunoregulatory and differentiation potential of mesenchymal stem cells (MSCs), we aimed to outline current insights into the clinical application of MSCs in COVID-19 patients. Based on results from preliminary clinical investigations, it can be predicted that MSC therapy for patients infected with SARS-CoV-2 is safe and effective, although multiple clinical trials with a protracted follow-up will be necessary to determine the long-term effects of the treatment on COVID-19 patients.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , COVID-19/therapy , Humans , Mesenchymal Stem Cell Transplantation/methods , SARS-CoV-2
19.
Stem Cell Res Ther ; 13(1): 283, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1910351

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild-moderate COVID-19-induced ARDS patients. METHODS: Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × [Formula: see text] cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. RESULTS: During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period. CONCLUSION: Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Control Groups , Cytokines , Humans , Iran , Mesenchymal Stem Cell Transplantation/methods , Pandemics , Respiratory Distress Syndrome/therapy
20.
Stem Cell Rev Rep ; 18(6): 2152-2163, 2022 08.
Article in English | MEDLINE | ID: covidwho-1877956

ABSTRACT

BACKGROUND: Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19. METHODS: A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated. RESULTS: Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia. CONCLUSIONS: Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020.


Subject(s)
COVID-19 , Exosomes , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Humans , Mesenchymal Stem Cell Transplantation/methods , Pilot Projects , SARS-CoV-2 , Umbilical Cord
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