Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises

Abstract

Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19.

Anosmia: a missing link in the neuroimmunology of coronavirus disease 2019 (COVID-19)

“…In such critical time, it is not difficult to remember the previous pandemics (Jabbari et al 2020), though none of the lessons learned could be satisfactory, revealing with the COVID-19 pandemic the limitation of national strategies and the need for reliable research and international collaboration (Kafieh et al 2020;Mohamed et al 2020a;Momtazmanesh et al 2020;Moradian et al 2020;Rzymski et al 2020). After the six-month effort, there is a lack of specific treatment and vaccine, though numerous efforts have taken place to find potential therapeutic and preventive options (Moazzami et al 2020;Rabiee et al 2020;Yazdanpanah et al 2020) from repurposing drugs (Mohamed et al 2020b) and the design and manufacturing of antibodies (Jahanshahlu and Rezaei 2020b) to the development of cell-based therapies (Basiri et al 2020). It is, therefore, mandatory to promote understanding of the pathogenesis of the disease.…”

COVID-19 and its Therapeutics: Special Emphasis on Mesenchymal Stem Cells Based Therapy

“…MSCs are currently investigated in various animal models and clinical trials for their immunotherapeutic potential. As COVID-19 pandemic was initiated in China, most of the studies are performed in association with Chinese institute [80][81][82] but as this pandemic escalated to other parts of the world, recently some nations, for instance, United State of America, Jordon, Brazil, and Spain, have started exploring the immunomodulatory potential of MSCs in clinical trials (Table 4) [ 83,84,86]. Zikuan Leng and co-workers [4] have performed a study on SARS-CoV-2 infected patients to investigate the potential of MSCs transplantation.…”

“…List of MSCs based clinical trials performed in different countries for the treatment of COVID-19[83][84][85] …”

Cell-Free Therapies: Novel Approaches for COVID-19

“…Moreover, important factors should be taken into consideration such as the culture medium, cell and tissue source, donor variability, and culture conditions (cell priming with hypoxia, biochemical or mechanical stimuli, three-dimensional spheroid culture, among others), as well as the timing and method of MSC-secretome harvesting (20,22). In short, cell-free therapies could be a more suitable treatment for COVID-19 than MSCs, but additional investigations are required (2).…”

“…EV biochemistry varies according to composition and cell source (41). EVs can carry membrane and cytosolic proteins, transcription factors, DNA, coding and non-coding RNAs and various signal transduction molecules (5,21,38,42), acting on both physiological and pathological events, e.g., modulating the inflammatory response (2,14). EVs also carry different cytokines and growth factors, such as interleukin (IL)-6 and IL-10, transforming growth factor (TGF)-β, and hepatocyte growth factor (HGF) (43).…”