Unraveling the therapeutic effects of mesenchymal stem cells in asthma

Abstract

Asthma is a chronic inflammatory disease associated with airway hyper-responsiveness, chronic inflammatory response, and excessive structural remodeling. The current therapeutic strategies in asthmatic patients are based on controlling the activity of type 2 T helper lymphocytes in the pulmonary tissue. However, most of the available therapies are symptomatic and expensive and with diverse side outcomes in which the interruption of these modalities contributes to the relapse of asthmatic symptoms. Up to date, different reports highlighted the advantages and beneficial outcomes regarding the transplantation of different stem cell sources, and relevant products from for the diseases’ alleviation and restoration of injured sites. However, efforts to better understand by which these cells elicit therapeutic effects are already underway. The precise understanding of these mechanisms will help us to translate stem cells into the clinical setting. In this review article, we described current knowledge and future perspectives related to the therapeutic application of stem cell-based therapy in animal models of asthma, with emphasis on the underlying therapeutic mechanisms.

C-Kit+ Cells Can Modulate Asthmatic Condition via Differentiation Into Pneumocyte-Like Cells and Alteration of Inflammatory Responses via ERK/NF-κB Pathway

“…Murine pulmonary C-Kit + cells are eligible to restore lung function by reducing the release of Th2 pro-in ammatory cytokines; IL-4, -5, and − 13, coincided with an elevation of type 2 macrophage IL-10 [37]. The ndings of the current study comply with previous studies, suggesting the immunomodulatory effect of C-Kit + cells in in vivo conditions by the promotion of phenotype shifting in macrophages from a proin ammatory state to an anti-in ammatory condition [50].…”

Enhancer-priming in ageing human bone marrow mesenchymal stromal cells contributes to immune traits

“…BMSC transplantation as a therapeutic option in animal models of asthma strongly indicates the immunosuppressive function of BMSCs in alleviating asthamtic symptoms (Mirershadi et al, 2020). The results here ( Figure 4E ), together with our observation of age-sensitive genes and peaks enrichment in immune-related traits ( Figure 4A-D ), strongly indicate that age-dependent priming of BMSC differentiation could simultaneously alter the immune-regulatory pathways shared, contributing to altering the bone marrow niche environment.…”

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

“…Indeed, several clinical trials on MSC-based therapy are currently being conducted for such diseases ( Regmi et al, 2019 ). With regard to asthma, many studies with different animal models have explored the therapeutic potential of MSCs in asthma ( Mirershadi et al, 2020 ; Srour and Thebaud, 2014 ). They show that MSCs not only attenuate pathological remodeling in the asthmatic lung, they also suppress the lung inflammatory responses.…”

“…Specifically, MSCs reduce eosinophilic inflammation, AHR, collagen fiber deposition, and serum IgE levels and regulate the Th1:Th2 ratio ( Inamdar and Inamdar, 2013 ; Nemeth et al, 2010 ; Zeng et al, 2015 ; Zhang and He, 2019 ). However, as described recently by the review of Mirershadi et al (2020) , these studies used different asthma models and their MSC treatment protocols markedly vary in terms of dose, timing, and route. Thus, the optimal MSC treatment regimens for specific types of asthma remain unclear.…”