Transplantation of Mesenchymal Stem Cells: A Potential Adjuvant Therapy for COVID-19

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen for coronavirus disease-2019 (COVID-19), which has posed an increasing serious public health threat. However, still there are no approved antiviral agents or vaccines available yet. Mesenchymal stem cells (MSCs) are emerging as a novel promising adjuvant therapy for the attenuation of COVID-19 based on its putative pathogenesis. MSCs may exert anti-inflammatory, immunomodulatory, anti-apoptotic, as well as regenerative effects through a series of mechanisms. Remarkably, MSCs may be resistant to virus infection, which is fundamental for the treatment of COVID-19. The beneficial therapeutic effects of MSCs have been preliminarily proved to be safe and efficacious for the treatment of COVID-19 in current clinical trials. This work aims to review the beneficial effects of MSCs in treating ALI/ARDS, which provides novel insight into the potential therapeutic strategies against COVID-19. However, further research is warranted regarding both safety and efficacy of MSCs.

Immunotherapy Summary for Cytokine Storm in COVID-19

“…MSC treatment of COVID-19 is safe and well-tolerated, and has shown good efficacy in shortening the course of the disease, reducing lung injury, and lowering cytokine levels (Meng et al, 2020;Yip et al, 2020;Häberle et al, 2021;Shi et al, 2021). The underlying mechanism of MSC in the treatment of COVID-19 is not elucidated, but current clinical evidence suggests that MSCbased therapy has the potential to be a supporting strategy (Zhu, et al, 2020).…”

“…Since the end of 2019, novel coronavirus has been gradually spread worldwide, which not only poses a severe challenge to the global public health system but also brings huge economic losses to the society. Virus infection can cause cytokine storm, and then lead to acute respiratory distress syndrome (ARDS), and even multiple organ failure until death (Zhu et al, 2020).…”

COVID-19 Pathology on Various Organs and Regenerative Medicine and Stem Cell-Based Interventions

“…Accordingly, by inhibiting the proliferation of T and B cells and by successful regulation of pro-inflammatory cytokines to optimize the microenvironment for intrinsic recovery, MSCs can reduce the cytokine storm. On the other hand, as the indirect effects to attenuate cytokine storm, they can restrict the innate immune system cell infiltration and consequently decrease the secretion of inflammatory cytokines ( Ellison-Hughes et al, 2020 ; Gupta et al, 2020 ; Zhu et al, 2020 ; Jeyaraman et al, 2021 ; Figure 2 ). 6 days after MSC therapy, cytokine storm-related immunity cells were showed to have dwindled.…”

“…Cytokine storm as the hallmark of COVID-19 severity is the increasing level of pro-inflammatory cytokines that can lead to organ failure and death. The immune-regulatory effects of mesenchymal stem cells on various cell types of the innate and adaptive immune system can attenuate cytokine storm in severe COVID-19 cases ( Lee and Song, 2018 ; Wang et al, 2018 ; Zhu et al, 2020 ).…”

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells

“…During a cytokine storm, the roles of cytokines in the immune response are complex, showing characteristics of a network, and these cytokines play roles in inducing local inflammation, promoting disease progression, regulating cellular and molecular immune responses, eliminating infection, and regulating tissue repair ( 14 ). Cytokine storms can cause serious damage to the body, such as hyaline membrane formation, diffuse alveolar injury, and fibrin exudation, and then accelerate lung injury, while serious lung injury and cytokine storms in the circulatory system further induce multiple organ dysfunction and injury throughout the body ( 15 , 16 ). At present, it is believed that the cause of severe pneumonia is not the virus itself but the excessive immune response induced by infection, and an unbalanced cytokine response in the body is an important cause of pneumonia and acute lung injury ( 17 ).…”