Autologous bone marrow-derived mononuclear cell therapy in three patients with severe asthma​

Abstract

Background: Despite recent advances in understanding its pathophysiology and development of novel therapies, asthma remains a serious public health issue worldwide. Combination therapy with inhaled corticosteroids and long-acting β2-adrenoceptor agonists results in disease control for many patients, but those who exhibit severe asthma are often unresponsive to conventional treatment, experiencing worse quality of life, frequent exacerbations, and increasing healthcare costs. Bone marrow-derived mononuclear cell (BMMC) transplantation has been shown to reduce airway inflammation and remodeling and improve lung function in experimental models of allergic asthma. However, to date, no study has evaluated the therapeutic effects of BMMCs in patients with severe asthma. Methods: This is a case series of three patients who presented with severe asthma unresponsive to conventional therapy and omalizumab. All received a single intravenous dose of autologous BMMCs (2×107) and were periodically evaluated for 1 year after the procedure. Endpoint assessments included physical examination; quality of life questionnaires; imaging (computed tomography, single-photon emission computed tomography, and ventilation/perfusion scan); lung function tests; and a 6-min walk test.Results: All patients completed the follow-up protocol. No serious adverse events attributable to BMMC transplantation were observed during or after the procedure. Lung function remained stable throughout. A slight increase in ventilation of the right lung was observed on day 120 after BMMC transplantation in one patient. All three patients reported improvement in quality of life in the early post-procedure course. Conclusions: This paper is the first to describe the effects of BMMC therapy in patients with severe asthma, providing a basis for subsequent trials to assess efficacy.

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

“…MSC-derived EV therapy is able to upregulate IL-10 and transforming growth factor-β1 (TGF-β1), which in turn are responsible for the recruitment and expansion of regulatory T cells ( Du et al, 2018 ), decrease the number of eosinophils in both lung tissue and BALF while also modulating airway remodeling ( de Castro et al, 2017 ), and mitigate T H 2/T H 1-induced lung inflammation and airway hyperresponsiveness ( Cruz et al, 2015 ). A recent clinical study demonstrated that administration of bone marrow-derived mononuclear cells was well-tolerated and safe and improved some quality of life parameters in three patients with severe asthma ( Aguiar et al, 2020 ). Two clinical studies (NCT02192736 and NCT03137199) designed to evaluate the potential therapeutic actions of MSCs and their trophic factors in individuals with severe asthma are ongoing.…”

Emerging Cell-Based Therapies in Chronic Lung Diseases: What About Asthma?

“…However, there are still some issues that must be addressed before translating this therapy to humans. To the best of our knowledge, there is only one study ( Aguiar et al, 2020 ) that demonstrated the potential efficacy of MSCs in patients with asthma and one ongoing clinical trial (NCT03137199). However, these studies ( Aguiar et al, 2020 ) have limitations, such as a small sample size with no placebo-control and inflammatory biomarkers.…”

“…To the best of our knowledge, there is only one study ( Aguiar et al, 2020 ) that demonstrated the potential efficacy of MSCs in patients with asthma and one ongoing clinical trial (NCT03137199). However, these studies ( Aguiar et al, 2020 ) have limitations, such as a small sample size with no placebo-control and inflammatory biomarkers. Procedures for cell culture need to be appropriately standardized to produce a satisfactory number of cells and should be proliferative and maintain their regeneration properties.…”