Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice

Abstract

There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs themselves in mitigating Th2/Th17-mediated allergic airway inflammation in a mouse model of severe refractory clinical asthma. Moreover, human MSC CM and extracellular vesicles were effective in this immunocompetent mouse model. These data add to a growing scientific basis for initiating clinical trials of MSCs or extracellular vesicles derived from MSCs in severe refractory asthma and provide further insight into the mechanisms by which the MSCs may ameliorate the asthma.

Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales

“…Potentially related to their immune suppressive effects, MSC-derived EVs (MSC-EVs) exert beneficial therapeutic effects in animal models for different diseases, including acute kidney failure, myocardial infarction, ischemic stroke and asthma [16–21]. Furthermore, MSC-EVs have been successfully used to treat a steroid-resistant Graft- versus -host disease (GvHD) patient without inducing any side effects [14].…”

CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

“…Normal, adult human lung fibroblasts (HLF) (catalog number CCL-199; ATCC, Manassas, VA, http://www.atcc.org) were expanded in culture with Dulbecco’s Modified Eagle Medium: Nutrient Mixture F-12 (Sigma-Aldrich, St. Louis, MO, https://www.sigmaaldrich.com), 10% FBS, 1% Pen/Strep, and 2 mM l -glutamine and used at passage 6 or lower. We have previously demonstrated that HLFs can be successfully used as a control cell population in immunocompetent mouse models of allergic airway inflammation [16, 19, 20]. …”

“…The ameliorating effects occur when the MSCs are administered either during initial antigen sensitization or at the onset of or during antigen challenge [9–20]. Some data also suggest that MSC administration can also protect against chronic or delayed antigen challenges [9, 18].…”

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

“…A dose-dependent inhibitory effect of MSC-derived extracellular vesicles on B-cell proliferation, differentiation and Ig production has been reported [58]. In a mouse model of severe refractory asthma, MSC-derived extracellular vesicles were as potent as the MSCs themselves in mitigating allergic airway inflammation [79]. In a model of hypoxia-induced pulmonary hypertension, treatment with MSC-derived exosomes ameliorated pulmonary hypertension and suppressed inflammation and alternative macrophage activation [80].…”