RESUMO
BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. METHODS: To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. RESULTS: No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. CONCLUSION: The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.
Assuntos
Células-Tronco Mesenquimais , Doença Pulmonar Obstrutiva Crônica , Medula Óssea , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de VidaRESUMO
Adult stem/progenitor cells are found in different human tissues. An in vitro cell culture is needed for their isolation or for their expansion when they are not available in a sufficient quantity to regenerate damaged organs and tissues. The level of complexity of these new technologies requires adequate facilities, qualified personnel with experience in cell culture techniques, assessment of quality and clear protocols for cell production. The rules for the implementation of cell therapy centers involve national and international standards of good manufacturing practices. However, such standards are not uniform, reflecting the diversity of technical and scientific development. Here standards from the United States, the European Union and Brazil are analyzed. Moreover, practical solutions encountered for the implementation of a cell therapy center appropriate for the preparation and supply of cultured cells for clinical studies are described. Development stages involved the planning and preparation of the project, the construction of the facility, standardization of laboratory procedures and development of systems to prevent cross contamination. Combining the theoretical knowledge of research centers involved in the study of cells with the practical experience of blood therapy services that manage structures for cell transplantation is presented as the best potential for synergy to meet the demands to implement cell therapy centers.
RESUMO
Adult stem/progenitor cells are found in different human tissues. An in vitro cell culture is needed for their isolation or for their expansion when they are not available in a sufficient quantity to regenerate damaged organs and tissues. The level of complexity of these new technologies requires adequate facilities, qualified personnel with experience in cell culture techniques, assessment of quality and clear protocols for cell production. The rules for the implementation of cell therapy centers involve national and international standards of good manufacturing practices. However, such standards are not uniform, reflecting the diversity of technical and scientific development. Here standards from the United States, the European Union and Brazil are analyzed. Moreover, practical solutions encountered for the implementation of a cell therapy center appropriate for the preparation and supply of cultured cells for clinical studies are described. Development stages involved the planning and preparation of the project, the construction of the facility, standardization of laboratory procedures and development of systems to prevent cross contamination. Combining the theoretical knowledge of research centers involved in the study of cells with the practical experience of blood therapy services that manage structures for cell transplantation is presented as the best potential for synergy to meet the demands to implement cell therapy centers.
Assuntos
Humanos , Células-Tronco , Técnicas de Cultura de Células , Boas Práticas de Fabricação , Células-Tronco Adultas , Terapia Baseada em Transplante de Células e TecidosRESUMO
Este estudo constitui uma análise do desempenho do teste sorológico treponêmico ELISA Recombinante Wiener lab. e de seis testes não treponêmicos (Laborclin: VDRL Bras. RPR Bras e RPR TRUST: Wama: VDRL e RPR; Wiener:USR) na triagem sorológica de doadores de sangue. Os resultados repetidamente reagentes (RR) foram confirmados por meio de três testes treponêmicos: FTAabs (Wama), WB (in house) e TPHA (bioMérieux). Foram analisadas 2990 amostras de soro. O teste VDRL (USR), utilizado inicialmente na triagem sorológica, apresentou reatividade em 11 (0,4por cento) amostras, com títulos variando de 1/1 até 1/32. Nos demais testes não treponêmicos, observou-se reatividade em um número de amostras que variou de 4 a 14, num total de 20 (0,7por cento) amostras das 2990 analisadas. O teste treponêmico ELISA apresentou resultados RR em 42 (1,4por cento) das amostras analisadas, entre as quais 8 (0,3por cento) se mostraram reagentes a, pelo menos, um teste não treponêmico. Das 42 amostras RR pelo teste ELISA submetidas aos testes confirmatórios de FTA-abs, TPHA e WB, 9 (21,4por cento) foram negativas para os três testes, 8 (19,1por cento) foram positivas para WB e TPHA e negativas para o FTA-abs e 25 (59,5por cento) foram positivas para os três testes. A especificidade do teste ELISA atingiu 99,7por cento, considerando-se o WB e o TPHA como confirmatórios. As 12 amostras que apresentaram resultados não reagentes no teste ELISA, mas mostraram algum tipo de reatividade para os testes não treponêmicos, tiveram resultado negativo nos testes confirmatórios utilizados. Mesmo que o descarte de bolsas seja maior quando se utiliza teste treponêmico, essa conduta parece ser a mais segura na triagem sorológica de doadores de sangue.