Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation

Abstract

Mesenchymal stem cell (MSC) research has demonstrated the potential of these cells to modulate lung inflammatory processes and tissue repair; however, the underlying mechanisms and treatment durability remain unknown. Here, we investigated the therapeutic potential of human bone marrow-derived MSCs in the inflammatory process and pulmonary remodeling of asthmatic BALB/c mice up to 14 d after transplantation. Our study used ovalbumin to induce allergic asthma in male BALB/c mice. MSCs were injected intratracheally in the asthma groups. Bronchoalveolar lavage fluid (BALF) was collected, and cytology was performed to measure the total protein, hydrogen peroxide (H2O2), and proinflammatory (IL-5, IL-13, and IL-17A) and anti-inflammatory (IL-10) interleukin (IL) levels. The lungs were removed for the histopathological evaluation. On day zero, the eosinophil and lymphochte percentages, total protein concentrations, and IL-13 and IL-17A levels in the BALF were significantly increased in the asthma group, proving the efficacy of the experimental model of allergic asthma. On day 7, the MSC-treated group exhibited significant reductions in the eosinophil, lymphocyte, total protein, H2O2, IL-5, IL-13, and IL-17A levels in the BALF, while the IL-10 levels were significantly increased. On day 14, the total cell numbers and lymphocyte, total protein, IL-13, and IL-17A levels in the BALF in the MSC-treated group were significantly decreased. A significant decrease in airway remodeling was observed on days 7 and 14 in almost all bronchioles, which showed reduced inflammatory infiltration, collagen deposition, muscle and epithelial thickening, and mucus production. These results demonstrate that treatment with a single injection of MSCs reduces the pathophysiological events occurring in an experimental model of allergic asthma by controlling the inflammatory process up to 14 d after transplantation.

Effects of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Future Perspectives

“…Bronchial asthma is one of the most common and chronic lung diseases in children and adults, whose pathophysiology is underpinned by a chronic inflammation of the airway walls accompanied by mucus hypersecretion, epithelial shedding, metaplasia and hyperplasia of goblet cells, increased collagen deposition, and hypertorophy and hyperplasia of airway smooth-muscle [69,70]. The current treatments for asthmatic patients are largely symptomatic and ineffective, and diverse side effects of these therapies has led researchers and clinicians to seek safe and effective candidates for this chronic disease.…”

“…Boldrini-Leite et al have found that in the ovalbumin (OVA)-induced asthma BALB/c mice model, the MSCtreated group is able to reduce the amount of eosinophil, lymphocyte, total protein, H 2 O 2 , IL-5, IL-13 and IL-17a in the BALF [71]. Similarly, Abreu et al and Song et al have demonstrated that MSCs are capable of reducing lung inflammation and tissue remodeling through promoting the production of anti-inflammatory cytokines and angiogenic factors (IL-4, IL-13, TGF-β, VEGF, VCAM-1, ICAM-1) [72,73], activating TGF-β signaling to induce M2-like macrophage polarization [74], decreasing oxidative stress, the thickness of basement membrane, epithelium, subepithelial and smooth muscle layer as well as the number of mast cells and goblet cells [75][76][77].…”

Mesenchymal Stem Cells Suppress Severe Asthma by Directly Regulating Th2 Cells and Type 2 Innate Lymphoid Cells

“…In previous studies, MSCs were transferred into murine models of asthma via the intravenous or intratracheal route ( Boldrini-Leite et al, 2020 ; Sun et al, 2012 ). However, these studies did not assess the effect of MSC on the immune response of naïve lungs.…”

Recent Findings on Cell-Based Therapies for COVID19-Related Pulmonary Fibrosis

“…In animal studies, MSCs have shown potential in treating acute lung injury, ARDS, asthma, and fibrosis 32 ; their mechanisms of action might include the inhibition of inflammatory cytokines, such as TNFa 33,34 . Thus, based on the passive defense method, virus-infected cells release interferons (IFNs) and stimulate genes like p21 to restrain cell growth.…”