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).
BackgroundChronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. ObjectiveThis article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. MethodsFour patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. ResultsThe results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. ConclusionsDespite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.
Células-tronco; terapia celular; pulmão; doença pulmonar obstrutiva crônica (DPOC); enfisema; fibrose cística. Introdução: células-tronco e terapia celular Células indiferenciadas que apresentam capacidade de autoduplicação e de dar origem a células diferenciadas são denominadas células-tronco (CT). 1 Melton e Cowan (2004) propuseram uma working definition de CT: "Uma entidade clonal autorrenovável, que é pluripotente e pode dar origem a vários tipos de células diferenciadas". 2 Apesar de variações conceituais, há dois aspectos básicos e comuns presentes nas mais diferentes definições de CT:
Scaffolds of chitosan and collagen can offer a biological niche for the growth of adipose derived stem cells (ADSC). The objective of this work was to characterize the physico-chemical properties of the scaffolds and the ADSC, as well as their interactions to direct influences of the scaffolds on the behavior of ADSC. The methodology included an enzymatic treatment of fat obtained by liposuction by collagenase, ASDC immunophenotyping, cell growth kinetics, biocompatibility studies of the scaffolds analyzed by the activity of alkaline phosphatase (AP), nitric oxide (NO) determination by the Griess-Saltzman reaction, and images of both optical and scanning electron microscopy of the matrices. The extent of the crosslinking of genipin and glutaraldehyde was evaluated by ninhydrin assays, solubility tests and degradation of the matrices. The results showed that the matrices are biocompatible, exhibit physical and chemical properties needed to house cells in vivo and are strong stimulators of signaling proteins (AP) and other molecules (NO) which are important in tissue healing. Therefore, the matrices provide a biological niche for ADSC adhesion, proliferation and cells activities.
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