Mesenchymal stem/stromal cell-based therapies for severe viral pneumonia: therapeutic potential and challenges

Abstract

Severe viral pneumonia is a significant cause of morbidity and mortality globally, whether due to outbreaks of endemic viruses, periodic viral epidemics, or the rarer but devastating global viral pandemics. While limited anti-viral therapies exist, there is a paucity of direct therapies to directly attenuate viral pneumonia-induced lung injury, and management therefore remains largely supportive. Mesenchymal stromal/stem cells (MSCs) are receiving considerable attention as a cytotherapeutic for viral pneumonia. Several properties of MSCs position them as a promising therapeutic strategy for viral pneumonia-induced lung injury as demonstrated in pre-clinical studies in relevant models. More recently, early phase clinical studies have demonstrated a reassuring safety profile of these cells. These investigations have taken on an added importance and urgency during the COVID-19 pandemic, with multiple trials in progress across the globe. In parallel with clinical translation, strategies are being investigated to enhance the therapeutic potential of these cells in vivo, with different MSC tissue sources, specific cellular products including cell-free options, and strategies to ‘licence’ or ‘pre-activate’ these cells, all being explored. This review will assess the therapeutic potential of MSC-based therapies for severe viral pneumonia. It will describe the aetiology and epidemiology of severe viral pneumonia, describe current therapeutic approaches, and examine the data suggesting therapeutic potential of MSCs for severe viral pneumonia in pre-clinical and clinical studies. The challenges and opportunities for MSC-based therapies will then be considered.

Key Role of Mesenchymal Stromal Cell Interaction with Macrophages in Promoting Repair of Lung Injury

“…In addition to the above described effects, antiviral properties have also been attributed to MSCs and MSC-EVs. MSCs could inhibit virus replication and shedding through IDO and LL37 secretion and improve influenza-induced viral pneumonia and ARDS due to anti-inflammatory and reparative potential, partly through the interaction with Mφ [ 182 , 183 ].…”

RGD-Hydrogel Improves the Therapeutic Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Phosgene-Induced Acute Lung Injury in Rats

“…RGD-hydrogel improved MSC survival but not cell engraftment in the lung. This result varied with the orthotopic transplantation of exogenous MSCs into dense tissues, such as ischemic myocardium [ 33 ] and injured brain [ 34 ], which could be attributed to the insufficient adhesion between the cells and lung lacunar parenchyma [ 35 ]. Hence, RGD-hydrogel has the potential to enhance lung injury repair by increasing MSC secretion and survival.…”

Safety and efficacy of clinical-grade, cryopreserved menstrual blood mesenchymal stromal cells in experimental acute respiratory distress syndrome

“…It is worth mentioning that clinical and pilot uncontrolled trials based on MSCs experienced an explosive increase due to the global pandemic of COVID-19 (Khoury et al, 2020). The systematic reviews and meta-analyses examining clinical studies based on the use of MSCs for COVID-19 ARDS agree that MSCs were safe, showed no detection of serious adverse events and were associated with a reduction in mortality and time to recovery compared to controls (Masterson et al, 2021;Chen et al, 2022;Kirkham et al, 2022).…”