Research

The Role and Potential Application of Immunomodulatory Mesenchymal Stem Cells in COVID- 19 Disease

Code:

L3-3176

Range:

01. October 2021 - 30. September 2024

Range:

0,25 FTE

Leader:

Janja Zupan

Field:

3.01 Medical sciences/ Microbiology and immunology

Abstract:

The declared pandemic caused by new SARS-CoV-2 virus in 2020, did not catch the research organizations and pharmaceutical companies completely unprepared. Many scientific groups have already carried out research that was indirectly addressing the challenges facing the international health systems of today. In Slovenia, high level of scientific and professional health care facilities have quickly re-organized their activities to fight against coronavirus pandemic. In the proposed translational project, collaborating partners from basic research teams at Faculty of Pharmacy and Medical Faculty of University of Ljubljana, National Institute of Biology along with clinical institution Blood Transfusion Centre of Slovenia and the company, Educell, d.o.o., have joined their forces to focus on the most critical healthrelated issue of COVID-19 disease. Namely, patients who develop this deadly pneumonia suffer from acute respiratory distress syndrome (ARDS). Despite being treated with aggressive mechanical ventilation, the mortality among these patients is between 30 and 60%. Even patients with a favorable outcome following ARDS, later experience severe problems due to lung tissue fibrosis and significantly impaired respiration, so the problem and the side effects remain long after the infection. Here, we propose an alternative and/or adjuvant treatment of ARDS using allogenic mesenchymal stem cells therapy. The aim of the biotechnology part of this proposal is to investigate and target the biological phenomenon caused by the SARS-CoV-2 virus, i.e. the rapid release of inflammatory molecules, so-called "cytokine storm". The "cytokine storm" is caused by secreted interferons and interleukins by infected epithelial cells that attract neutrophils and other inflammatory cells. Acute inflammation causes edema, lung damage, and obstruction of breathing, due to an imbalance of oxygen exchange. Among the potential therapeutic options for reducing the clinical and biological picture of extensive inflammation is the use of immunosuppressive mesenchymal stem cells (MSCs), which are already used in some ARDS syndromes of other pathological origin. The MSC manufacturing technology started in April 2020 by the American company NantKwest, Inc that received the FDA approval for the treatment of patients with COVID-19 disease. Cooperating with NantKwest, Educell d.o.o, is adopting powerful next-generation bioengineering for the biopharmaceutical production of the developed therapeutic populations of MSCs isolated from healthy donors. The aim of the scientific part of the proposed project is to identify key features of MSC immunosuppression and defining yet unknown variables of various inter-cellular MSC interactions in SARS-CoV-2-infected lung tissue associated with “cytokine storm”. The aim for clinical benefit of MSCs treatment in COVID-19 ARDS patients is to:
1.) reduce mortality and contribute to faster patient recovery,
2.) prevent the death toll by the potential next wave of disease due to lethal viral mutants,
3.) reduce the healthcare burden due to lack of the equipment and overloaded medicalpersonnel.