Fetal Smoke Exposure and Emphysema: Role of Stem Cells

Summary

Principal Investigator: Stephen Rennard
Abstract: [unreadable] DESCRIPTION (provided by applicant): COPD is currently the fourth leading cause of death. It is a complex condition characterized by progressive airflow limitation resulting from emphysema and airway disease. Cigarette smoking is the major cause, but 20% of cases develop in non-smokers and smokers have varying degrees of susceptibility. Emphysema, which is characterized by lung tissue destruction, is thought to result from injury caused by smoke. Tissue destruction, however, represents an imbalance between tissue injury and the capacity of tissues to repair. Recent evidence suggests that early life events can contribute to COPD risk. Among these, exposure to cigarette smoke has been demonstrated to be a risk factor, and evidence supports the concept that maternal environmental smoke exposure is sufficient. The current proposal will test the hypothesis that fetal exposure as a result of maternal environmental smoke exposure leads to a defect in the maintenance of stem/precursor cells in the lung. As a result, the lung is unable to maintain repair functions with age and, as such, is predisposed to develop senile emphysema. This increased susceptibility to develop emphysema is exacerbated by exposure to smoke-induced injury in adulthood. This hypothesis will be tested by exposing pregnant mice to levels of smoke consistent with environmental exposures. Pups will then be monitored for lung cell repair functions and susceptibility to develop emphysema as they age. The role of stem cells will be evaluated by quantifying progenitor stem/cell functions in the exposed animals using in vivo and in vitro methods. Bone marrow (stem cell) transplants will be used to confirm the role of stem cells and to attempt to restore lung function. This will establish fetal environmental smoke exposure as a cause of adult COPD and provide a novel basis for therapy. [unreadable] [unreadable]
Funding Period: 2005-05-02 - 2009-03-31
more information: NIH RePORT

Top Publications

  1. pmc Long-term cigarette smoke exposure in a mouse model of ciliated epithelial cell function
    Samantha M Simet
    Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE 68198 5910, USA
    Am J Respir Cell Mol Biol 43:635-40. 2010
  2. ncbi Governmental, national, international agency and other initiatives to advance the application of cellular therapies
    J G Sharp
    Cytotherapy 7:315-6. 2005
  3. pmc Natural histories of chronic obstructive pulmonary disease
    Stephen I Rennard
    University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198 5885, USA
    Proc Am Thorac Soc 5:878-83. 2008

Scientific Experts

  • S Rennard
  • Samantha M Simet
  • J G Sharp
  • Joseph H Sisson
  • Craig Boyer
  • Shin Kawasaki
  • Xiangde Liu
  • Todd A Wyatt
  • Jane M Devasure
  • John G Sharp
  • Jacqueline A Pavlik

Detail Information

Publications3

  1. pmc Long-term cigarette smoke exposure in a mouse model of ciliated epithelial cell function
    Samantha M Simet
    Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE 68198 5910, USA
    Am J Respir Cell Mol Biol 43:635-40. 2010
    ..In parallel with the slowing of CBF, significant PKC activation from cytosol to the membrane of tracheal epithelial cells was detected in mice exposed to smoke for 6-12 months...
  2. ncbi Governmental, national, international agency and other initiatives to advance the application of cellular therapies
    J G Sharp
    Cytotherapy 7:315-6. 2005
  3. pmc Natural histories of chronic obstructive pulmonary disease
    Stephen I Rennard
    University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198 5885, USA
    Proc Am Thorac Soc 5:878-83. 2008
    ..With advances in understanding the clinical features of COPD and with the development of evaluating new tools to assess patients with COPD, longitudinal studies evaluating COPD in novel ways and for longer durations are needed...