Stem cells treat COVID-19 complications

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by a coronavirus (SARS-CoV-2). COVID-19 primarily affects the lungs as well as other organ systems, including the heart and immune system. The receptor for the coronavirus are angiotensin-converting enzyme molecules, which are especially abundant in the lungs, blood vessels, heart, and digestive tract.


Excessive activation of the immune system by SARS-CoV-2 virus is characterized by increased release of pro-inflammatory cytokines, so-called cell “hormones”, which enhance inflammatory reactions and connective tissue synthesis. This phenomenon is called “cytokine storm”. The level of pro-inflammatory cytokines correlates with the severity of the disease.


Damage to the cells of the pulmonary alveoli (alveocytes) and vascular endothelium (endotheliocytes) in COVID-19 leads to pulmonary edema, atelectasis (collapse of bronchus) thrombosis, the development of respiratory distress syndrome, which in turn causes dysfunction of internal organs. Interstitial pneumonia, which develops in COVID-19, is accompanied by thickening of the interalveolar septa, the development of connective tissue in the lungs, which replaces the functionally active lung tissue.


Although the causes of COVID-19 and the pathological changes that develop in this disease are well described, a literally effective treatment protocol has not yet been developed, in different patients the course of the disease is very different. Doctors are no less concerned about postcovid syndrome (“chronic” COVID) in people who have laboratory recovery.


At the beginning of the COVID-19 epidemic in China, several high-profile cases of overcoming complications of COVID-19 in critically severe patients using umbilical cord mesenchymal stem cells were reported. This treatment approach has been adopted by scientists from other countries, and by the end of 2020, clinical trials using mesenchymal stem cells in COVID-19 have been reported in the United States, China, Spain, Colombia, the United Kingdom, Pakistan, Mexico, Belgium, Brazil, France, Germany, Belarus, Iran, Jordan, Turkey, UAE, Canada, South Korea, Indonesia, Ukraine, Egypt, Sweden, Russia.


In the treatment of COVID-19 mesenchymal stem cells of the umbilical cord, placenta, bone marrow, umbilical cord blood, adipose tissue, dental pulp, nasal mucosa, menstrual blood are used. Cell drugs are preferably administered intravenously, once or twice/thrice. Doses of mesenchymal stem cells range from 1 x 106 / kg / injection to 10 x 106 / kg / injection.


Clinical trials on the treatment of COVID-19 with stem cells worldwide have been initiated by biotechnology companies such as Athersys, Cynata, Mesoblast and Pluristem.


Experience with the use of mesenchymal stem cells in the treatment of COVID-19 today indicates their safety, and in many patients have high therapeutic efficacy was noted. Mesenchymal stem cells reduce the production of perhaps the main proinflammatory cytokine – tumor necrosis factor-alpha, increase the synthesis of interleukin-4, which has an immunomodulatory effect in COVID-19. Thus, mesenchymal stem cells reduce the “cytokine storm”, protect the epithelial cells of the alveoli, promote regeneration.


Due to the immunomodulatory and regenerative properties of mesenchymal stem cells, they have been used in the treatment of respiratory distress syndrome, as well as a number of autoimmune diseases (multiple sclerosis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis).


Mesenchymal stem cells in COVID-19 increase the activity of B-lymphocytes, which increases antibody production, as well as regulatory dendritic cells, M2 macrophages, regulatory T-lymphocytes, while reducing the activity of M1-macrophages and neutrophilic granulocytes, whose increased activation in COVID-19 is undesirable. Mesenchymal stem cells also reduce collagen synthesis, which reduces the level of interstitial pneumonia, have a positive effect on the function of epithelial and endothelial cells.


The world experience of using mesenchymal stem cells in the treatment of COVID-19 is summarized in the article by Zhongwen Li et al “Stem cell therapy for COVID-19, ARDS and pulmonary fibrosis”, published in 2020 in the international scientific journal “Cell Proliferation”.


In particular, a group of 7 patients with COVID-19 was reported, in whom 2 days after the introduction of mesenchymal stem cells significantly reduced symptoms, increased the number of lymphocytes in the peripheral blood, decreased levels of C-reactive protein, which is an important marker of inflammation.


In another observation group, 64% of patients after mesenchymal stem cell therapy showed clinical improvement, confirmed by computed tomography of the lungs.


In Ukraine, doctors and scientists at the Institute of Cell Therapy have developed a method of treating coronavirus pneumonia using mesenchymal placental stem cells. In March 2020, in conjunction with Kiev City Clinical Hospital №4, a clinical trial “Treatment of coronavirus COVID-19 pneumonia (SARS-CoV-2) with cryopreserved allogeneic multipotent mesenchymal placental stem cells” was launched under the auspices of the Coordination Center of Transplantation of Organs, Tissues and Cells of Ukraine.


The Clinic of the Institute of Cell Therapy also offers a program of postcovid rehabilitation of patients who have recovered from COVID-19, because most patients after laboratory recovery have long been observed to have a dysfunction of the nervous system, respiratory system, cardiovascular system and other disorders. The comprehensive program of postcovid rehabilitation at the Institute of Cell Therapy is aimed at the rapid return of the patient to a full life.


Sources: Zhongwen Li et al. Stem cell therapy for COVID-19, ARDS and pulmonary fibrosis. Cell Proliferation. 2020; 53: e12939, also used data from the Association of Cryobanks.


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