Experimental Basis and New Insights for Cell Therapy in Chronic Obstructive Pulmonary Disease

Abstract

Chronic Obstructive Pulmonary Disease (COPD) can be briefly described as air flow limitation and chronic dyspnea associated to an inflammatory response of the respiratory tract to noxious particles and gases. Its main feature is the obstruction of airflow and consequent chronic dyspnea. Despite recent advances, and the development of new therapeutic, medical and clinical approaches, a curative therapy is yet to be achieved. Therapies involving the use of tissue-specific or donor derived cells present a promising alternative in the treatment of degenerative diseases and injuries. Recent studies demonstrate that mesenchymal stem cells have the capacity to modulate immune responses in acute lung injury and pulmonary fibrosis in animal models, as well as in human patients. Due to these aspects, different groups raised the possibility that the stem cells from different sources, such as those found in bone marrow or adipose tissue, could act preventing the emphysematous lesion progression. In this paper, it is proposed a review of the current state of the art and future perspectives on the use of cell therapy in obstructive lung diseases.

Mesenchymal Stem Cells: A Promising Therapy for the Acute Respiratory Distress Syndrome

“…Several studies have demonstrated the potential therapeutic effect of MSCs in different diseases: myocardial infarction [41,42,43,44], pulmonary fibrosis [45,46], pulmonary hypertension [47,48,49,50], emphysema [51,52,53], diabetes [54], sepsis [55,56], asthma [57], hepatic failure [58], acute renal failure [59] and ARDS [5,38,60,61,62,63,64]. In all preclinical studies, infused MSCs expanded in vitro were used.…”

Terapia celular em modelo experimental do enfisema pulmonar induzido por meio de fumaça de cigarro.

“…Há vários estudos na literatura que mostram a migração celular para o pulmão, após a infusão de células em vasos periféricos (Adachi et al, 2006;Faria et al, 2012;Katsha et al, 2011;Kotton et al,2001;Krause et al, 2001;Lama et al,2007;Longhini-dos-Santos et al, 2013;Neuringer, Radell, 2004;Pereira et al,1995;Ribeiro-Paes et al, 2009, 2011, 2012Schrepfer et al, 2007;Sueblinvong, Weiss, 2010;Suratt et al,2003;Yamada et al,2004). Células infundidas na circulação periférica são levadas diretamente para o pulmão, o que torna esta estratégia de infusão passível de ser aplicada em modelos experimentais e terapia celular experimental em pacientes humanos.…”

“…Desta forma, muitos modelos animais de DPOC têm sido propostos por diferentes grupos de pesquisadores que buscam uma maior compreensão da fisiopatologia, bem como alternativas que sejam eficazes no tratamento do enfisema (Cazzola et al, 2007;Faria et al, 2012;Fusco et al, 2002;GOLD, 2009;Gross et al, 1965;Hele, 2002;Hyatt et al, 2000;Longhini-dos-Santos et al, 2013;Mahadeva, Shapiro, 2002;Martorana et al, 1989;Nikula et al , 2000;Ribeiro-Paes et al, 2009, 2011, 2012.…”

“…Embora os métodos de indução de enfisema pulmonar não reproduzam perfeitamente a patologia humana, novas metodologias de indução foram propostas, como instilação por via intratraqueal e intranasal de proteases (papaína e elastase), exposição à fumaça de cigarro e modelos genéticos, visando contribuir para uma melhor compreensão da fisiopatologia da DPOC (Brusselle et al, 2006;Faria et al, 2012;Fox, Fitzgerald, 2004;Fusco et al, 2005;Hele, 2001;Longhini-dos-Santos et al, 2013;Mahadeva, Shapiro, 2002;Nikula et al 2000;Ribeiro-Paes et al, 2012;Rubio et al, 2004;Zhang et al, 2009). …”

“…Alguns estudos demonstram que o grau do enfisema está relacionado à dosagem administrada ao animal (Antunes, Rocco, 2011;Faria, 2012;Kawakami et al, 2008;Lüthje et al, 2009). Ministrando doses repetidas de elastase em tempos pré determinados, Lüthje et al…”