Susan M Krisinski Majka, PhD
Assistant Professor
School of Medicine
Charles C. Gates Regenerative Medicine and Stem Cell Biology Program
Section of Cardiology
University of Colorado Denver (UCDenver)
12800 E 19th Ave
PO Box 6511, Rm 8125
Mail Stop 8320
Aurora, CO 80045
Phone: 303 724-3957
Fax: 303 724 3051
E-Mail: Susan.Majka@ucdenver.edu
The goal of our work is to understand the role resident lung mesenchymal stem cells play in the development of lung diseases, specifically the genesis of myofibroblasts. It is important to study the role of stem cells in the context of lung disease and their regulation by the microenvironment.
Because stem cells have the characteristic of self-renewal they have the potential to exponentially generate offspring with proliferative capacity not characteristic of terminally differentiated cells.
We have developed an isolation/enrichment procedure that is based on the ability of primitive progenitor cells to efflux a Hoechst dye via an ABCG2 transporter. The ability to efflux this dye is common to many different types of adult stem cells, termed the side population or SP.
We have recently demonstrated on a clonal level that the lung SP of cells contains a bona fide mesenchymal stem cell population with great potential of self-renewal as demonstrated by high levels of telomerase and long telomeres. Our studies will exploit the new insights into the molecular and cellular basis of lung SP stem cell participation in the pathogenesis of lung diseases, both adult and pediatric, from our mouse models for therapeutic purposes.
Pulmonary hypertension (PAH), chronic obstructive pulmonary disease (COPD), interstitial pulmonary fibrosis (IPF) and other adult lung conditions are a major cause of morbidity and mortality. Deaths due to these conditions have doubled in the last decade.
Chronic lung disease (CLD) affects the cardiovascular and pulmonary systems following treatment of premature newborns, during later stages if lung development, with mechanical ventilation and oxygen therapy. It is characterized by the disruption of alveolar and vascular development and decreased alveolar and vascular density.
Increased inflammation, increased acquisition of the myofibroblast cell phenotype and changes in contractile properties of pulmonary vasculature and airways is paramount in the pathogenesis of these lung diseases. The relationship between inflammation, myofibroblast accumulation and loss of pulmonary function with regard to stem cell differentiation has not been defined.
This interplay between pulmonary stem cells and development of disease is the focus of our research.
There is an increasing emphasis on the development of cell-based therapies to address these conditions, but the lung is a recalcitrant candidate for these strategies because of the diverse cell types and functions as well as a lack of understanding of how chronic disease processes affect stem cell differentiation. Therefore, prior to testing cell-based therapy, it is desirable to use pre-clinical animal models of lung injury and chronic disease to determine how changes in the lung tissue during the development of disease affect resident stem cell differentiation and function.
Selected Peer-Reviewed Publications:
S. Majka , M. Skokan, J. Harral, S. Gladson, K. Stenmark, J. Lloyd, L. Wheeler, M. Garcia and J. West. A Role for Progenitors in Vascular Remodeling During Pulmonary Arterial Hypertension. AJP Lung Cell Mol Physiol. 10/08 ePub
J. Martin, K. Helm, P. Ruegg, M. Garcia, E. Burnham and S. Majka. Adult Lung Side Population Cells have Mesenchymal Stem Cell Potential. Cytotherapy 2008 10:140-151.
D. Irwin, K. Helm, N. Campbell, M. Imamura, K.Fagan, J. Harral, M. Carr, K.A. Young D. Klemm, S. Gebb, E.C. Dempsey, J. West and S. Majka. 2007. Neonatal lung SP cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplification. AJP:LCMP . 293(4):L941-51.
D. Case, D. Irwin, C. Ivestor, J Harral, K. Morris, M. Imamura, M. Roedersheimer, A. Patterson, M. Carr, M. Hagen, M. Saavedra, J. Crossno Jr., K. Young, E. Dempsey, F. Poirier, J. West and S. Majka. 2007. Galectin-1 Dependent Vascular Remodeling in Pulmonary Hypertension. AJP Lung Cell Mol Physiol. 292:L154-164.
J. Crossno, S. Majka, T. Grazia, R. Gill and D. Klemm. 2006. Rosiglitazone Promotes Formation of Multilocular Adipocytes from Bone Marrow Progenitor Cells. JCI 116:3220-3228.
S. Majka , M. Beutz, M. Hagen, A Izzo, N. Voelkel and K. Helm. 2005. Invited Review. Adult Pulmonary Stem Cells: The Lung SP Population. Stem Cells. Stem Cells 23:1073-1085.
S. Majka , K.J.Jackson, K.A. Kienstra, M.W. Majesky, M.A. Goodell and K.Hirschi. 2003. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. JCI (1) 111:71-79.