RESUMO
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRß) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRß+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRß+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFß activation in primary human skeletal muscle and cardiac PDGFRß+ cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.
Assuntos
Integrina alfaV/metabolismo , Músculo Esquelético/patologia , Miocárdio/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Animais , Apoptose , Movimento Celular , Células Cultivadas , Colágeno/metabolismo , Fibrose , Genótipo , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Recombinantes/metabolismoRESUMO
Access to human tissue is critical to medical research, however the laws and regulations surrounding gaining ethical and legal access to tissue are often poorly understood. Recently, there has been a huge increase in the interest surrounding the therapeutic application of adipose tissue, and adipose-derived stem cells. To facilitate our own research interests and possibly assist our local colleagues and collaborators, we established a Research Tissue Bank (RTB) to collect, store and distribute human adipose tissue derived cells with all the appropriate ethical approval for subsequent downstream research. Here we examine the legal, ethical and practical issues relating to the banking of adipose tissue for research in the UK, and discuss relevant international guidelines and policies. We also share our experiences of establishing an RTB including the necessary infrastructure and the submission of an application to a Research Ethics Committee (REC).