Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

Abstract

Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 · 10 6 cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the APinjured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA.

Intranasal administration of mesenchymoangioblast‐derived mesenchymal stem cells abrogates airway fibrosis and airway hyperresponsiveness associated with chronic allergic airways disease

“…For IV administration of MCA‐MSCs, 1 × 10 7 cells were resuspended in 2 ml PBS. Mice were restrained in a Perspex restrainer (Perspex Distribution, Chelmsford, United Kingdom), and 1 × 10 6 cells/200 μl PBS were injected into the tail vein of Sal‐ or Ova‐sensitized/challenged mice, which is a commonly used cell concentration delivered to mice (13, 15, 20, 28). For IN administration of MCA‐MSCs, 1 × 10 7 cells were resuspended in 0.5 ml of PBS.…”

“…As such, MSCs can be administered systemically via intravenous (IV) infusion, allowing for a broad distribution (12). Upon administration, MSCs accumulate in the lung (13). MSCs also home to the injured tissue through the expression of the chemokine receptor type 4, and the expression of this receptor is heightened in a proinflammatory environment such as in asthma, enhancing their homing ability (14).…”

Long‐term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma

“…Adipose‐derived MSCs were chosen for this study as previous studies have demonstrated that adipose‐derived MSCs are easier to culture in large numbers and share a similar phenotype to bone marrow‐derived MSC . In addition, several studies have demonstrated that adipose‐derived MSCs are capable of reducing airway inflammation, airway hyperresponsiveness, and Th2 cytokine production in a murine model [unpublished data] . Prior to performing this study, the effects of MSCs in an acute model of experimental asthma were assessed longitudinally in a pilot study [unpublished data].…”

Effects of storage culture media, temperature and duration on human adipose‑derived stem cell viability for clinical use

“…ADSCs are characterized by low immunogenicity and the adaptation of ADSCs to their environment provides a promising direction for future clinical applications (31). Martinez-Gonzalez et al (32), demonstrated that ADSCs protect the alveoli structure in patients with asthma by reducing the inflammation generated by neutrophil granulocytes, reducing IgE secretion and inhibiting lymphocyte infiltration. Additionally, Won et al (33) revealed that local injection of ADSCs promoted hair growth.…”