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

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)

New methodologies for old problems: tridimensional gastrointestinal organoids and guts-on-a-chip

Objectives: The present review intended to present a critical overview of the methodological and experimental advances concerning tridimensional cell culture models within the scope of gastrointestinal research. Methods: A literature review was performed and some of the main published articles in the area were mentioned. Main results: Classic studies and high impact results were presented, starting from the pioneer works with gastrointestinal organoids, with a small gut organoid, to the achievement of guts-on-a-chip and multi-organ-chips. It was also discussed which implications the construction of such co-cultures bring, as well as future applications arising from these new methodologies. Conclusions: Despite the still discrete number of publications, in quantitative terms, there are qualitative promising and consistent results addressing physiopathological aspects and new therapeutic perspectives of tridimensional in vitro cultures in the gastroenterology field. It is expected, thus, that such new methodological approaches, including organoids and guts-on-a-chip, may contribute decisively to the advance in knowledge on basic aspects, as well as on the translation to new therapeutic approaches in gastrointestinal diseases. Resumo: Objetivos: A presente revisão visou apresentar uma abordagem crítica dos avanços metodológicos e experimentais referentes a modelos de cultura celular tridimensionais no âmbito do sistema gastrintestinal. Métodos: Foi realizada revisão da literatura com ênfase nos principais artigos publicados na área. Resultados principais: São apresentados trabalhos clássicos e resultados de maior impacto, desde os trabalhos pioneiros com organoides do sistema gastrintestinal, com intestino delgado, até a obtenção de guts-on-a-chip e multi-organ-chips. Discutiu-se, ainda, as implicações decorrentes da elaboração de tais co-culturas, bem como as futuras aplicações decorrentes dessas novas metodologias. Conclusões: Apesar do número ainda discreto de publicações, em termos quantitativos, há, qualitativamente, resultados promissores e consistentes abordando aspectos fisiopatológicos e de novas perspectivas terapêuticas em gastrenterologia decorrentes das culturas tridimensionais in vitro. É esperado, portanto, que essas novas abordagens metodológicas incluindo organoides e guts-on-a-chip possam contribuir decisivamente para o avanço no conhecimento sobre de aspectos básicos, bem como para a translação do conhecimento para novas abordagens terapêuticas em doenças gastrintestinais. Keywords: Organoids, Organs-on-a-chip, Gut-on-a-chip, In vitro tridimensional models, Gastrointestinal, Palavras-chave: Organoides, Organs-on-a-chip, Gut-on-a-chip, Modelos in vitro tridimensionais, Gastrintestina

Levantamento epidemiológico das parasitoses intestinais: viés analítico decorrente do tratamento profilático

As parasitoses intestinais constituem um grave problema de saúde pública, especialmente nos países subdesenvolvidos, sendo esse problema associado e agravado por condições sanitárias precárias e falta de informação. Neste trabalho foram avaliados alguns parâmetros epidemiológicos vinculados às principais enteroparasitoses em diferentes regiões da cidade de Assis, Estado de São Paulo, Brasil. Os dados foram confrontados com aqueles obtidos em um levantamento anterior referente ao ano de 1991 e apresentam uma redução de três pontos percentuais. Há indícios de que, antiparasitários estariam sendo distribuídos profilaticamente, antes dos resultados do exame parasitológico de fezes. Este fato pode levar a importantes implicações epidemiológicas e distorções analíticas. Esta conduta terapêutica pode estar ocultando condições sanitárias e/ou educacionais desfavoráveis, de forma que haveria uma baixa prevalência de parasitoses em razão de reiterados tratamentos e não pela melhoria das condições de saneamento básico e educação sanitária da população.Intestinal parasite infections are a serious public health problem, mainly in underdeveloped countries, and are usually associated with (and aggravated by) poor sanitation and lack of information. This study evaluated a series of epidemiological parameters associated with the main intestinal parasites in different areas of the city of Assis, São Paulo State, Brazil. The data were compared with those obtained from a previous survey in 1991 and showed a reduction of three percentage points. There is evidence of prophylactic dispensing of drugs for parasites, before receiving the results of stool tests. This could have important epidemiological implications and lead to analytical distortions. This therapeutic approach could disguise unfavorable health and/or educational conditions, with a low prevalence of parasite infections due to repeated treatments rather than improvements in basic sanitation and health education for the population

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

BACKGROUND Chronic 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. OBJECTIVE This 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. METHODS Four 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. RESULTS The 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. CONCLUSIONS Despite 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