iPSC‐ and mesenchymoangioblast‐derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid

Abstract

The airway remodeling (AWR) associated with chronic allergic airways disease (AAD)/asthma contributes to irreversible airway obstruction. This study compared and combined the antiremodeling and other effects of induced pluripotent stem cell and mesenchymoangioblast‐derived mesenchymal stem cells (MCA‐MSCs) with the corticosteroid dexamethasone (Dex) in experimental chronic AAD/asthma. Female BALB/c mice subjected to 11 wk of ovalbumin (Ova)‐induced chronic AAD were intranasally administered MCA‐MSCs (1 × 106 cells/mouse; once weekly on wk 10 and 11), Dex (0.5 mg/ml; once daily for 2 wk), or both combined. MCA‐MSC detection and changes in airway inflammation (AI), AWR, and airway hyper‐responsiveness (AHR) were measured at the end of wk 11. Mice with chronic AAD had significant AI, goblet cell metaplasia, epithelial damage/thickening, aberrant TGF‐β1 levels, subepithelial myofibroblast accumulation, airway/lung fibrosis, and AHR (all P < 0.001 vs. healthy controls). MCA‐MSCs were detected in the lungs up to 5–7 d postadministration and demonstrated modest anti‐inflammatory but striking antifibrotic effects against Ova‐induced AAD, effectively decreasing AHR by 70–75% (all P < 0.05 vs. Ova alone). In comparison, Dex predominantly demonstrated anti‐inflammatory effects, decreasing AHR by ∼30%. Combining MCA‐MSCs with Dex provided equivalent protection to that offered by either therapy alone. MCA‐MSCs reduce chronic AAD‐induced AWR and AHR to a greater extent than Dex and may act as a suitable adjunct therapy to corticosteroid treatment of asthma.—Royce, S. G., Mao, W., Lim, R., Kelly, K., Samuel, C. S. iPSC‐ and mesenchymoangioblast‐derived mesenchymal stem cells provide greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid. FASEB J. 33, 6402–6411 (2019). http://www.fasebj.org

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study

“…Although initially tested in aGVHD, iPSC-derived MSCs may be used in the future for a range of other clinical targets. Encouraging data on the potential utility of iPSC-derived MSCs manufactured using this platform have already been generated in preclinical models of critical limb ischemia 33 , asthma 34,35 , organ transplant rejection 36 and acute respiratory distress syndrome 37 . Furthermore, we note that primary MSCs have been investigated for a wide range of other therapeutic indications, and we hypothesize that iPSC-derived n, number of patients; first response, improvement by at least one aGvHD grade; best response, maximal improvement in aGvHD grade.…”

IL-1β augments TGF-β inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics

“…And the effect of LTRA on attenuate airway remodeling by inhibiting TGF-β/Smad signaling has been also demonstrated [ 36 ]. However, recent studies have also focused on the ineffective of glucocorticoid in treating airway remodeling [ 37 , 38 ]. Our results showed that neither glucocorticoid or montelukast sodium can reverse the changes of EMT markers induced by TGF-β1/IL-1β.…”

Cell motility and migration as determinants of stem cell efficacy

“…However, this notion is counterbalanced by the fact that human MSC and NSC can reach the brain after intranasal administration in immunocompetent rodent models of brain disorders [ 12 , 51 ]. Moreover, intranasally administered human MSC derived from clinical-grade human iPSC line were shown to provide greater protection than corticosteroids against allergic airways disease in mice [52] . Intranasally applied NSC have also been successfully delivered to the brain in a model with strong local, i.e.…”