Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives

Abstract

Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases

“…These findings have opened up the discussion about the convenience of therapies based on ASC or their cell products, such as their conditioned medium (CM) or extracellular vesicles (EV). At this moment, therapies that use ASC have adequately progressed to clinical practice; however, the appropriateness of treatments that are based on their products are still under debate until the nature of their components are fully defined and the methods for their isolation are standardized [ 32 , 33 , 34 ]. In this sense, it exists a wide variety of mediators that have been identified by different research groups in ASC-derived CM, with critical regulatory factors that are present in some studies but absent in others; undoubtedly, this is a research area of high interest.…”

Activated Mesenchymal Stromal Cell Therapy for Treatment of Multi-Drug Resistant Bacterial Infections in Dogs

“…Given that human MSC appear to generate higher direct antimicrobial activity, and respond better to activation, it may be plausible to consider the effectiveness of the activated MSC treatment strategy for difficult to treat chronic, drug resistant infections in humans, combined with antibiotic therapy. Several clinical trials have reported previous or ongoing work to evaluate MSC for treatment of acute infections, including bacterial pneumonias ( 14 , 46 ). Therefore, it would be informative to consider similar studies of activated allogeneic MSC therapy for recalcitrant infections, including soft tissue infections and deep bone infections, in humans.…”

Phosgene-Induced acute lung injury: Approaches for mechanism-based treatment strategies

“…Therefore, MSCs have been introduced as a potential treatment for ALI and other pneumonia-associated diseases ( 86 , 87 ). MSCs redistribute to inflammatory tissues and organs ( 88 , 89 ) and play a protective role by targeting the lesion location, adopting an epithelium-like phenotype, and alleviating inflammation and collagen deposition during ALI and ARDS ( 90 , 91 ). In addition to immunomodulatory effects, MSCs also differentiate into pulmonary epithelial cells and endothelial cells, which function in the repair of the blood barrier and blood gas recovery ( 92 ).…”