An extracorporeal device, named selective cytopheretic device (SCD), has been fabricated that sequesters activated leukocytes and inhibits their release of inflammatory proteins and cytokines. Leukocytes are major contributors to the pathogenesis and progression of many clinical inflammatory disorders, including the systemic inflammatory response syndrome (SIRS), sepsis and acute respiratory distress syndrome (ARDS). A large number of therapeutic approaches are under investigation to limit the activation and tissue accumulation of leukocytes at sites of inflammation in order to minimize tissue destruction and disease progression. This research proposal will evaluate this SCD on a well-developed porcine model of septic shock, SIRS and early ARDS. Various cardiovascular parameters, systemic cytokine levels, and pulmonary inflammation with bronchoalveolar lavage (BAL) parameters and time to death will be compared between treatment and sham treatment groups. The effects of membrane surface area and efficacy of a simplified circuit system on the ongoing multiorgan dysfunction and inflammatory processes will also be assessed. This proposal may suggest a manner of altering the systemic inflammatory response and may lead to a new therapeutic approach to sepsis, SIRS and ARDS. ? ? ? ?
|Pino, Christopher J; Yevzlin, Alexander S; Lee, Kyungsoo et al. (2013) Cell-based approaches for the treatment of systemic inflammation. Nephrol Dial Transplant 28:296-302|
|Westover, Angela J; Buffington, Deborah A; Humes, H D (2012) Enhanced propagation of adult human renal epithelial progenitor cells to improve cell sourcing for tissue-engineered therapeutic devices for renal diseases. J Tissue Eng Regen Med 6:589-97|
|Pino, Christopher J; Yevzlin, Alexander S; Tumlin, James et al. (2012) Cell-based strategies for the treatment of kidney dysfunction: a review. Blood Purif 34:117-23|
|Ding, Feng; Song, Joon Ho; Jung, Ju Young et al. (2011) A biomimetic membrane device that modulates the excessive inflammatory response to sepsis. PLoS One 6:e18584|