Pilot safety study of intrabronchial instillation of bone marrow-derived mononuclear cells in patients with silicosis

Marcelo M Morales, Sérgio A L Souza, Luiz Paulo Loivos, Marina A Lima, Amir Szklo, Leandro Vairo, Taís H K Brunswick, Bianca Gutfilen, Miquéias Lopes-Pacheco, Alberto J Araújo, Alexandre P Cardoso, Regina C Goldenberg, Patricia R M Rocco, Lea M B Fonseca, José R Lapa e Silva, Marcelo M Morales, Sérgio A L Souza, Luiz Paulo Loivos, Marina A Lima, Amir Szklo, Leandro Vairo, Taís H K Brunswick, Bianca Gutfilen, Miquéias Lopes-Pacheco, Alberto J Araújo, Alexandre P Cardoso, Regina C Goldenberg, Patricia R M Rocco, Lea M B Fonseca, José R Lapa e Silva

Abstract

Background: Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis.

Methods: We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18-50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s <60 % and >40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 × 10(7) cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation.

Results: No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration.

Conclusion: Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. CLINICAL TRIALS.

Gov identifier: NCT01239862 Date of Registration: November 10, 2010.

Figures

Fig. 1
Fig. 1
Evolution of quality of life domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health), as measured by the SF-36 questionnaire, during the 360 days follow-up period. All parameters remained stable throughout the observation period. Values are median (25th–75th percentile) of 5 patients at each time point
Fig. 2
Fig. 2
a Representative image of whole-body scintigraphy showing the biodistribution of 99mTc-labeled BMDMCs 2 h after instillation in one patient; stem cells are seen mainly in the lungs. b There is also uptake in the mouth and stomach, due to minor swallowing during instillation. RL, right lung; LL, left lung; BMDMCs, bone marrow–derived mononuclear cells; 99mTc-BMDMCs, 99mTc-labeled bone marrow–derived mononuclear cells
Fig. 3
Fig. 3
Representative image of CT and 99mTc-BMDSC SPECT showing correspondence of a left lung lesion (green triangular area). CT, computed tomography; 99mTc-BMDSC, 99mTc-labeled bone marrow–derived mononuclear cells; SPECT, single-photon emission computed tomography
Fig. 4
Fig. 4
a 99mTc-macroaggregated albumin perfusion scintigraphy sequences from before cell therapy until 360 days after cell therapy, showing normal uptake at the right base and decreased uptake at both apexes. Improvement in the left base can be seen from day 120 to day 360. b Values are median (25th–75th percentile) of 5 patients at each time point. Statistical analysis of lung perfusion, showing significant differences mainly in the base of the right lungs from day 30 to day 360 as compared with baseline. RL, right lung; LL, left lung

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