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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305911

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.

2.
Stem Cell Res Ther ; 12(1): 316, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1255964

ABSTRACT

Coronavirus disease 2019 (COVID-19) may result in a life-threatening condition due to a hyperactive immune reaction to severe acute respiratory syndrome-coronavirus-2 infection, for which no effective treatment is available. Based on the potent immunomodulatory properties of mesenchymal stromal cells (MSCs), a growing number of trials are ongoing. This prompted us to carry out a thorough immunological study in a patient treated with umbilical cord-derived MSCs and admitted to the Intensive Care Unit for COVID-19-related pneumonia. The exploratory analyses were assessed on both peripheral blood and bronchoalveolar fluid lavage samples at baseline and after cellular infusion by means of single-cell RNA sequencing, flow cytometry, ELISA, and functional assays. Remarkably, a normalization of circulating T lymphocytes count paralleled by a reduction of inflammatory myeloid cells, and a decrease in serum levels of pro-inflammatory cytokines, mostly of interleukin-6 and tumor necrosis factor-α, were observed. In addition, a drop of plasma levels of those chemokines essential for neutrophil recruitment became evident that paralleled the decrease of lung-infiltrating inflammatory neutrophils. Finally, circulating monocytes and low-density gradient neutrophils acquired immunosuppressive function. This scenario was accompanied by an amelioration of respiratory, renal, inflammatory, and pro-thrombotic indexes. Our results provide the first immunological data possibly related to the use of umbilical cord-derived MSCs in severe COVID-19 context.


Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , SARS-CoV-2 , Umbilical Cord
3.
Stem Cells ; 39(6): 707-722, 2021 06.
Article in English | MEDLINE | ID: covidwho-1121521

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has grown to be a global public health crisis with no safe and effective treatments available yet. Recent findings suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus pathogen that causes COVID-19, could elicit a cytokine storm that drives edema, dysfunction of the airway exchange, and acute respiratory distress syndrome in the lung, followed by acute cardiac injury and thromboembolic events leading to multiorgan failure and death. Mesenchymal stem cells (MSCs), owing to their powerful immunomodulatory abilities, have the potential to attenuate the cytokine storm and have therefore been proposed as a potential therapeutic approach for which several clinical trials are underway. Given that intravenous infusion of MSCs results in a significant trapping in the lung, MSC therapy could directly mitigate inflammation, protect alveolar epithelial cells, and reverse lung dysfunction by normalizing the pulmonary microenvironment and preventing pulmonary fibrosis. In this review, we present an overview and perspectives of the SARS-CoV-2 induced inflammatory dysfunction and the potential of MSC immunomodulation for the prevention and treatment of COVID-19 related pulmonary disease.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Mesenchymal Stem Cells/immunology , SARS-CoV-2/immunology , COVID-19/therapy , COVID-19/virology , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Humans , Immunomodulation , Lung/immunology , Lung/pathology , Lung/virology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/virology , Pandemics , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/therapy , Pulmonary Fibrosis/virology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2/genetics
4.
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
5.
Cytotherapy ; 22(5S): S3, 2020 05.
Article in English | MEDLINE | ID: covidwho-823480
6.
Cytotherapy ; 22(9): 474-481, 2020 09.
Article in English | MEDLINE | ID: covidwho-197744

ABSTRACT

Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.


Subject(s)
Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Adrenal Cortex Hormones/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/therapy , Humans , Immune Reconstitution Inflammatory Syndrome/etiology , Immune Reconstitution Inflammatory Syndrome/therapy , Immunization, Passive , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Killer Cells, Natural/immunology , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/therapy , Pandemics , Plasmapheresis , Pneumonia, Viral/physiopathology , STAT Transcription Factors/antagonists & inhibitors
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