The purpose of this study is to determine whether cell therapy with autologous adult stem cells (from bone marrow and/or fat) is safe in the treatment of advanced Chronic Obstructive Pulmonary Disease (COPD).

Pulmonary emphysema, within the spectrum of Chronic Obstructive Pulmonary Disease (COPD), can be described as the destruction of alveolar walls and enlargement of the airspaces distal to the terminal bronchioles, with inflammatory infiltrate and no detectable fibrosis. Despite significant advances resulting from the introduction of new therapeutic approaches, such as pulmonary rehabilitation, an effective and not only palliative clinical treatment is yet to be achieved. Surgical treatment, in turn, involves highly complex procedures and, in the case of lung transplantation, the shortage of donors. In this context, cell therapy with stem cells is presented as a promising therapeutic alternative with great potential for applicability. The main goal of this study is to evaluate the safety of the infusion of bone marrow mononuclear cells (BMMC), adipose-derived stem cells (ASC), separately or conjugated, in COPD patients. The sample will consist of 20 advanced COPD patients (grade 3 by GOLD criteria). Patients will be, by lot, divided into four distinct groups, namely: Group 1: Control; Group 2: Bone marrow mononuclear cells; Group 3 - Stem cells derived from adipose tissue and Group 4: bone marrow mononuclear cells and stem cells derived from adipose tissue. After the selection of patients, clinical and laboratory evaluation will be conducted (cardiology, laboratory examinations and tests to define the score of dyspnea). The cells used for the cell therapy will be obtained from the patient's own bone marrow or adipose tissue (autologous). The separation of the bone marrow mononuclear (BMMC) will be performed by centrifugation in density gradient (Ficoll), while stem cells derived from adipose tissue will be isolated by enzymatic digestion (collagenase) and cultivation. The infusion will be performed by a peripheral vein (brachial) after preparation, separation, expansion and quality control of the cells. The patients will be followed for a period of 12 months. It is expected that this clinical protocol will allow an expansion in knowledge about cell therapy in pulmonary diseases and represents a significant step towards the establishment of new therapeutic approaches in COPD treatment.

Inclusion Criteria:

• COPD patients with persistent dyspnea in stage 2 or 3 of the dyspnea scale score;
• Eligibility for pulmonary rehabilitation program;
• No smoking or smoking cessation for at least 6 months.

Exclusion Criteria:

• Absence of emphysema on chest tomography;
• Pulmonary or extrapulmonary infection or active infection history in less than 3 months;
• History of coronary artery disease and/or severe ventricular dysfunction (ejection fraction <55%);
• Presence of pulmonary hypertension, ie, estimated systolic pulmonary artery pressure above 35 mmHg at transthoracic Doppler echocardiography;
• Patients in home oxygen therapy;
• Advanced renal failure (serum creatinine greater than 1.5 mg / dL) and liver failure CHILD B or C;
• Immunosuppressive or infectious diseases detected;
• Patients with known malignancies or collagen diseases;
• Psycho-social problems, drug and/or alcohol abuse and not obedient to the established medical protocol;
• No family acceptance;
• Pregnancy or at risk of pregnancy.