Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

João Tadeu Ribeiro-Paes, Aldemir Bilaqui, Oswaldo T Greco, Milton Artur Ruiz, Monica Y Marcelino, Talita Stessuk, Carolina A de Faria, Mario R Lago, João Tadeu Ribeiro-Paes, Aldemir Bilaqui, Oswaldo T Greco, Milton Artur Ruiz, Monica Y Marcelino, Talita Stessuk, Carolina A de Faria, Mario R Lago

Abstract

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009).

Keywords: BMMC; cell therapy; chronic obstructive pulmonary disease COPD; pulmonary emphysema; stem cells.

Figures

Figure 1
Figure 1
Study design adopted for this unicentric clinical trial of cellular therapy in chronic obstructive pulmonary disease – pulmonary emphysema. Abbreviations: BMMC, bone marrow mononuclear cells; MRC, Modified Medical Research Council [Dyspnea Scale].
Figure 2
Figure 2
A) Forced expiratory volume in 1 sec (FEV1). B) Percentage of predicted FEV1 pre- and postprocedure, for IMC 002, IMC 003, and IMC 004 patients.
Figure 3
Figure 3
A) Forced vital capacity (FVC). B) Percentage of predicted FVC pre- and postprocedure.
Figure 4
Figure 4
Vital capacity (VC) pre- and postprocedure.

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