Since December 2019, Wuhan, China has been conducting surveillance for influenza and related diseases and a number of cases of viral pneumonia have been detected, all diagnosed as viral pneumonia or pulmonary infection. The World Health Organization (WHO) classified it as a novel coronavirus (2019-nCoV) on January 12, 2020.
The coronavirus research group dubbed the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO dubbed the condition it caused coronavirus disease 2019 (COVID-19).
Study: When Stem Cells Meet COVID-19: Current Advances, Challenges, and Future Prospects. Credit: Giovanni Cancemi/Shutterstock
Immune control and healing from tissue injury are important capabilities of stem cells, especially mesenchymal stem cells (MSCs). MSCs and lung stem/progenitor cells (LSCs) have been used extensively in the treatment of viral infections and diseases such as acute lung injury (ALI) in recent years. Since the outbreak of COVID-19, MSC therapy has also been in focus. In recent studies, MSCs have been found to be effective in attenuating the severe inflammatory response in SARS-CoV-2 patients, improving lung function, protecting and repairing the lungs, and playing a positive role in alleviating pulmonary fibrosis in COVID-19 patients.
In addition, numerous studies have established a variety of stem cell-derived organoids as an ideal and sufficient model to study the probability and mechanism of multi-organ infection by SARS-CoV-2, which can help clinical therapy research.
A group of researchers from multiple institutions address the role of stem cells in the fight against COVID-19 in this paper, which provides a systematic review and perspective of the study on stem cell-based therapy and disease modeling of COVID-19.
The use of stem cells for COVID-19 therapy
There are now numerous applications and studies for experimental stem cell therapy in critically ill COVID-19 patients, especially for MSC therapy. MSCs are produced from the mesoderm and ectoderm in the early stages of embryonic development and have received much press for their multidirectional differentiation ability, immunomodulatory abilities, and lack of ethical issues. MSCs have been extracted from many tissues and used for specific tissue repair and regeneration with the advance of regenerative medicine and precision medicine. MSCs can currently be extracted from a variety of human tissues including bone marrow, umbilical cord blood, adipose tissue, endometrium, uterine blood, embryos and so on.
The first study of stem cell treatment in COVID-19 found that intravenous administration of clinical-grade MSCs to 7 COVID-19 patients improved their functional outcomes and promoted rehabilitation. From January 23, 2020 to February 16, 2020, Beijing YouAn Hospital in China recruited 7 COVID-19 patients. Each patient received 1 x 106 MSCs per kg body weight by intravenous infusion. No acute infusion-related adverse events or allergic events were noted within two hours of transplantation. Patients had high fever, weakness, shortness of breath, and hypoxia prior to MSC transplantation. All symptoms had disappeared 2-4 days after transplantation and the lung function of all patients had greatly improved. Furthermore, according to this study, the lack of angiotensin converting enzyme 2 (ACE2) and the high expression of certain trophic factors could represent the immunomodulatory mechanism of MSCs.
MSCs show the greatest potential as a cell-based therapy for COVID-19 as they have significant immunoregulatory properties and can regulate both the innate and adaptive immune systems. To reduce overactive immune responses and cytokine storm syndrome (CSS), MSCs can release a variety of soluble substances as well as extracellular vesicles and exosomes (EXOs).
MSCs can also affect the intensity and balance of the immune response by directly interacting with immune cells such as lymphocytic T cells, B cells, macrophages, neutrophils, and natural killer (NK) cells. In addition, studies have found that adult cells only produce interferon when the virus invades, activating hundreds of antiviral genes and recruiting immune cells to fight the virus, while stem cells are independent of interferon and can continuously activate many antiviral genes.
Overall, despite the fact that clinical stem cell research is still in its infancy, stem cell treatment offers extensive clinical applications and far-reaching relevance thanks to ongoing exploration of clinical stem cell research and data mining. It is also expected that as stem cell therapy advances, more severely ill COVID-19 patients will be rescued and more lives will be saved.