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Activated stem cells in damaged lungs could be first step toward cancer
May 27, 2009DURHAM, N.C. - Stem cells that respond after a severe injury in the lungs of mice may be a source of rapidly dividing cells that lead to lung cancer, according to a team of American and British researchers.
"There are chemically resistant, local-tissue stem cells in the lung that only activate after severe injury," said Barry R. Stripp, Ph.D., professor of medicine and cell biology at Duke University Medical Center. "Cigarette smoke contains a host of toxic chemicals, and smoking is one factor that we anticipate would stimulate these stem cells. Our findings demonstrate that, with severe injury, the resulting repair response leads to large numbers of proliferating cells that are derived from these rare stem cells."
Stripp said this finding could be related to the increased incidence of lung cancer in people with chronic disease states, in particular among cigarette smokers.
The findings were published in the advance online edition of the Proceedings of the National Academy of Sciences during the week of May 25.
"On the positive side, I think that it might be possible to improve lung function in the context of disease if we could understand which pathways regulate lung stem cell activation and then target these pharmacologically," said lead author Adam Giangreco, Ph.D., from Cancer Research UK's Cambridge Research Institute. "In terms of lung cancer susceptibility, however, our observation that stem cell activation leads to clonal expansion after injury could, in the context of additional mutations, promote the development of cancerous or precancerous lesions from activated stem cells."
The scientists used a chimeric mouse model, part wild-type and part with green fluorescent protein-tagged cells (GFP), so that the behavior of different populations of duplicating lung cells could be evaluated with high-resolution imaging methods. By understanding the extent to which GFP-positive and GFP-negative cells were mixed, the investigators were able to show that the abundant population of progenitor cells that normally maintain the epithelial layer in the lung could be rapidly wiped out with a strong chemical, naphthalene. Then the rare proliferative cells became active and grew into large patches.
The researchers at Duke and Cancer Research UK used a unique whole-lung imaging method to examine and identify the location of stem cells in the lung tissue of mice, and determine the role they play in both healthy and damaged mouse lungs.
They found that, while the stem cells don't appear to be involved in the normal maintenance of healthy or moderately injured lungs, they do play a vital role in repairing severely damaged lungs.
Even though this repair mechanism is important for restoring lung function, it can come at a price. An acquired mutation in that rare cell or its descendants leads to clonal patches of many identical cells. Secondary mutations in any one of these cells may provide the signals needed for unregulated cell growth and tumor progression.
"This work provides a plausible mechanism to account for this type of event that we previously didn't have," Stripp said.
Duke University Medical Center
The findings were published in the advance online edition of the Proceedings of the National Academy of Sciences during the week of May 25.
"On the positive side, I think that it might be possible to improve lung function in the context of disease if we could understand which pathways regulate lung stem cell activation and then target these pharmacologically," said lead author Adam Giangreco, Ph.D., from Cancer Research UK's Cambridge Research Institute. "In terms of lung cancer susceptibility, however, our observation that stem cell activation leads to clonal expansion after injury could, in the context of additional mutations, promote the development of cancerous or precancerous lesions from activated stem cells."
The scientists used a chimeric mouse model, part wild-type and part with green fluorescent protein-tagged cells (GFP), so that the behavior of different populations of duplicating lung cells could be evaluated with high-resolution imaging methods. By understanding the extent to which GFP-positive and GFP-negative cells were mixed, the investigators were able to show that the abundant population of progenitor cells that normally maintain the epithelial layer in the lung could be rapidly wiped out with a strong chemical, naphthalene. Then the rare proliferative cells became active and grew into large patches.
The researchers at Duke and Cancer Research UK used a unique whole-lung imaging method to examine and identify the location of stem cells in the lung tissue of mice, and determine the role they play in both healthy and damaged mouse lungs.
They found that, while the stem cells don't appear to be involved in the normal maintenance of healthy or moderately injured lungs, they do play a vital role in repairing severely damaged lungs.
Even though this repair mechanism is important for restoring lung function, it can come at a price. An acquired mutation in that rare cell or its descendants leads to clonal patches of many identical cells. Secondary mutations in any one of these cells may provide the signals needed for unregulated cell growth and tumor progression.
"This work provides a plausible mechanism to account for this type of event that we previously didn't have," Stripp said.
Duke University Medical Center
Stem Cells Current Events and Stem Cells News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
The use of stem cells in regenerative medicine may also be detrimental for health
The use of stem cells in regenerative medicine is not always beneficial for human health, it may even be harmful according to a work done by the University of Granada and University of León. Scientists have demonstrated that transplantation of human mononuclear cells isolated from umbilical cord blood exerted a deleterious effect in rats with liver cirrhosis.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
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