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.

Methods: This is a case series of three patients who presented severe asthma, unresponsive to conventional therapy and omalizumab. They 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 described for the first time the effects of BMMC therapy in patients with severe asthma, providing a basis for subsequent trials to assess the efficacy of this therapy.

Keywords: Asthma; Autologous transplantation; Bone marrow mononuclear cells; Cell therapy; Lung.

Fig. 1

Representative images of fibroblast colony-forming unit assay. a Primary culture of BMMCs 14 days after plating. b Macroscopic image of cell culture plate after Giemsa staining. c Microscopic image of a single stained colony after 14 days in culture

Fig. 2

Imaging of patients 1 (upper panel) and 2 (lower panel). a, e Whole-body (WB) scintigraphy 2 h after intravenous administration of ^99mTc-BMMCs. Uptake found in the liver, lungs, heart, blood pool, kidney, and bladder. b, f Lung ventilation/perfusion SPECT/CT 28 days before BMMC transplantation. c, g^99mTc-BMMC SPECT/CT demonstrating liver and lung uptake 2 h after BMMC transplantation. d, h Lung ventilation/perfusion SPECT/CT 120 days after BMMC transplantation

Fig. 3

Evaluation of self-perceived quality of life (QoL) over the 1-year follow-up period, as measured by St. George’s Respiratory Questionnaire (SGQR)