Stem cell therapy for COVID‐19: Possibilities and challenges

Abstract

Since its eruption in China, novel coronavirus disease (COVID-19) has been reported in most of the countries and territories (>200) of the world with ∼18 million confirmed cases (as of August 3, 2020). In most of the countries, COVID-19 upsurge is uncontrolled with a significant mortality rate. Currently, no treatment effective for COVID-19 is available in the form of vaccines or antiviral drugs and patients are currently treated symptomatically. Although the majority of the patients develop mild symptoms and recover without mechanical ventilation for respiratory management, severe respiratory illness develops in a significant portion of affected patients and may result in death. While the scientific community is working to develop vaccines and drugs against the COVID-19 pandemic, novel alternative therapies may reduce the mortality rate. Recent use of stem cells for critically ill COVID-19 patients in a small group of patients in China and subsequent Emergency Use Authorization of stem cells by Food and Drug Administration to Global Institute of Stem Cell Therapy and Research and Athersys has created excitement among the medical community. As a result, several clinical trials have been registered using stem cells for COVID-19 treatment that aim to use different cell sources, dosage, and importantly diverse targeted patient groups. In this brief review, the possibilities of stem cell use in COVID-19 patients and relevant challenges in their use have been discussed.

The contributory role of lymphocyte subsets, pathophysiology of lymphopenia and its implication as prognostic and therapeutic opportunity in COVID-19

“…After infusion of MSCs, while there was a significant elevation in the number of peripheral lymphocytes, the serum levels of TNF-α and CRP were dropped down remarkably [76] . Choudhery et al also reported the success of MSC transplantation in diminishing the level of TNF‐α as well as elevating the serum level of IL-10 in critical cases of COVID-19 [145] . Incidentally, Rajarshia et al [146] and Golchin et al [147] found that MSCs may be possibly one of the most ideal therapeutics, or considered as a combinational treatment for COVID-19 patients.…”

“…Incidentally, Rajarshia et al [146] and Golchin et al [147] found that MSCs may be possibly one of the most ideal therapeutics, or considered as a combinational treatment for COVID-19 patients. It has been also reported that allogeneic bone marrow MSC-derived exosomes are enabled to reduce cytokine storm, restore oxygenation, and reconstruct the immune responses in the favor of the COVID-19 patients' survival [145] . All in all, the evidence supports the effectiveness of MSC products in the treatment of COVID-19 patients, as they may reduce pro-inflammatory cytokines and improve lymphopenia-related complications.…”

Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination

“…The produced MSCs for therapeutic applications should be evaluated considering the criteria recommended by the international society for cell therapy (ISCT). The presence of certain surface markers, analysis of protein content, secretome, MSC-EVs, and microRNAs should be approved by using standard assays before any therapeutic applications [ 93 , 94 ]. It seems that a reliable cell bank for production, quality control, and storage of standard MSC vials might compensate for these challenges in an emergency condition.…”

Treatment of COVID-19 by Stage: Any Space Left for Mesenchymal Stem Cell Therapy?

“…MSCs have been recently trialed for the treatment of severe COVID-19, the main indication being critically patients with the manifestation of ARDS (reviewed in [ 127 , 128 ]).…”