
Two acclaimed stem cell cloning experts from the University of Houston have reported new findings of abnormal cells in the lungs of patients who have idiopathic pulmonary fibrosis (IPF). The breakthrough results yield key targets in future treatment options for this pulmonary disease.
IPF is an advanced, terminal lung condition in which undefined mechanisms scar the lungs making breathing difficult. According to the University of Houston, “the most pervasive school of thought is that IPF arises from recurrent, subclinical lung injury that imparts changes to epithelial and stromal cells, which, in turn, compromise lung repair and favor fibrosis.”
Frank McKeon, MD, PhD, director of the Stem Cell Center and professor of biology and biochemistry, and Wa Xian, PhD, research associate professor at the center, decided to look closer. They studied lung tissue from patients who had transplant surgery for life-threatening lung disease, provided by Houston Methodist Lung Transplant Center. Using single cell cloning technologies, McKeon and Xian produced libraries of basal stem cells from 16 patients with IPF and 10 patients without the disease.
“We identified a major stem cell variant that was distinguished from normal stem cells by its ability to transform normal lung fibroblasts to pathogenic myofibroblasts in vitro and to activate and recruit myofibroblasts in clonal xenografts,” reported Drs. McKeon and Xian in Science Translational Medicine.
"This study breaks new ground by showing lung fibrosis is driven by specific basal stem cell variants that become overly abundant in diseased lungs,” said Howard J. Huang, MD, medical director of the Houston Methodist Lung Transplant Center. “Importantly, these variants are distinct from abnormal variants identified in other chronic lung diseases. These findings suggest therapies selectively targeting these pathogenic stem cell variants may ameliorate fibrotic lung disease progression."
Additional analysis of the variants will help researchers decipher specific risk factors for IPF in comparison to COPD and other pulmonary conditions. Even further, McKeon said, it will help advance treatment options in this field.