مقالات پذیرفته شده در پنجمین کنگره بین المللی زیست پزشکی
Exosome therapy for COVID-19 infection
Exosome therapy for COVID-19 infection
Mahsa Rahgoshay,1,*Amir Atashi,2Mansoureh Ajami,3Fatemeh Jamshidi,4
1. Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran 2. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
Introduction: first detected in Wuhan, China. Since December 2019, the outbreak of disease has become a serious global health threat. The number of confirmed Covid-19 patients stands at more than 220 million people globally, with over 4 million deaths and more than 200 million cases have recovered. COVID-19 primarily affects the lungs and the infection may progress and cause life-threatening complications induced by a cytokines storm including pneumonia, acute respiratory distress syndrome (ARDS), septic shock, multi-organ dysfunction, and even death. There are no specific antiviral medications for COVID-19 virus-infected patients to date. Finally, an effective vaccine will be required to offer protection against SARS-CoV-2 infection. However, with unprecedented efforts being made by scientists, few vaccines have been approved by the FDA. Although the vaccination protects the receiver from suffering a serious disease, there is no evidence so far that the vaccine prevents the virus from spreading indefinitely. In this regard, there is a rapid pace of clinical examinations to find promising therapeutic strategies for the disease.
Some approaches using human mesenchymal stem cells (MSCs) and/or MSC-derived Extracellular Vehicles (EVs) as a therapeutic solution for the treatment of severe COVID-19 patients. Although promising results of MSCs transplantation have been demonstrated extensively, this technique is restricted owning to cell viability, safety, scalability, and some regulatory problems, making it an impractical choice for millions of infected cases around the world. However, EVs secreted from MSC, a crucial set of signaling encapsulated vesicles, are novel, next-generation agents that have similar functions as their parent cells.
Methods: EVs may have a role in preventing the cytokine storm and also avoiding the suppression of antiviral defenses that were responsible for COVID-19 pathogenesis. Among EVs, the prominent roles of exosomes in different pathological conditions have been widely reported. Exosomes are membrane-bound EVs 30–120 nm in size and may be involved in both pathological and physiological conditions. In the last year, several pre-clinical studies have confirmed that EVs-based therapies, particularly MSC-derived exosomes (MSC-Exo), considerably attenuated pulmonary inflammation and improved the clinical function of damaged lungs in a rapid, and safer way. Moreover, MSC-Exo might play a crucial role in the control of acute respiratory impairment induced by coronaviruses. Multiorgan dysfunction has been seen in many infected patients with COVID-19. According to the clinical reports, MSC-Exo contains a variety of growth factors, cytokines, mRNA, and miRNA with regenerative potential and anti-inflammatory and immunomodulatory effects which can repair diverse experimental injury models like liver injury, CNS stroke, renal injury, cardiovascular, and various types of lung disease. Therefore, they could be a good tool to treat multiple organ dysfunction. Furthermore, sepsis is a key lethal disease in COVID-19 patients, and MSC-Exos has the potential to reduce the rate of death in animals with sepsis. Several studies have shown that miRNAs secreted by MSC-Exo like miR-145, miR-21, and let-7 accelerate lung recovery. Moreover, miRNA could change the expression of cell receptors and thus blocking RNA viruses like Coronavirus to enter the cells. A recent study by Sengupta et al. concluded that exosomes derived from bone marrow mesenchymal stem cells (ExoFlo™) could potentially treat severe COVID-19.
Results: The data revealed a survival rate of about 83%. 71 % of the cases recovered, 13 % remained critically ill, and 16 % expired for causes unrelated to therapy. Moreover, laboratory values have shown a reduction in C-reactive protein (CRP) and D-dimer concentration, with a remarkable improvement in neutrophil and lymphocyte count. Generally, exosomes may be considered as an alternative to MSCs, because they can readily cross the blood-brain barrier, are economical, and don’t undergo independent self-renewal, so avoiding adverse effects, such as tumor development.
Conclusion: Finally, although MSC-Exosomes appears to be an intriguing COVID-19 therapeutic agent, additional investigation is needed for their clinical application. Moreover, it is imperative to optimize exosome isolation, storage, optimum dosage, and route of administration for the treatment of COVID-19 patients. As a result, since MSCs have been researched more extensively in these fields than MSC-Exos, they are predominantly examined in COVID-19 clinical trials.