The process, created in the laboratory of Rick A. Wetsel, Ph.D., a professor of molecular medicine at the IMM, is described in this week’s edition of the Proceedings of the National Academy of Sciences (PNAS). Research scientist Dachun Wang, M.D., is lead author of the article, “A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.”
“We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells,” said Wetsel, noting the procedure also can be used to create other types of highly-specialized cells.
Scientists at the IMM used the in vitro method to create lung epithelial cells known as alveolar epithelial type II. The cells were derived from a human embryonic stem cell line approved by the National Institutes of Health (NIH).
The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene.
“It is a general technology for developing select cells from human embryonic stem cells,” said C. Thomas Caskey, M.D., the IMM’s chief operating officer, director and CEO-elect. “The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others.”
James T. Willerson, M.D., president of the UT Health Science Center at Houston, said " I believe this is an important development by the Wetsel laboratory at the IMM. I look forward to seeing its transitional impact."
Alveolar epithelial type II cells are called “the stem cells of the lungs” because of their versatility and many important functions. They produce proteins including surfactant that inflates lungs. They also make other cells lining the inner lung. “They regulate lung fluids and oxygen levels,” Wetsel said.
The cells are part of the tiny air sacs lining the lower airways known as alveoli. Tissue thin, they transfer oxygen into the blood and remove carbon dioxide. If the walls of the hundreds of millions of alveolus in a pair of lungs could be spread out and placed side by side, they would cover the floor of a classroom.
According to Wetsel, transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries. “These are the cells that can potentially be used for regenerative lung repair,” he said.
Hereditary lung disorders most likely to benefit from transplantation of alveolar epithelial type II cells include respiratory distress syndrome of the newborn, alpha-1 related emphysema and cystic fibrosis, Wetsel believes. “All three of these diseases are caused by single gene defects and therefore have been logical candidates for gene therapy,” Wetsel said.
Respiratory distress syndrome of the newborn, a condition affecting premature infants less than 37 weeks of age, may be caused by a genetic mutation triggering a surfactant shortage. Likewise, alpha-1 related emphysema, a condition affecting 100,000 Americans, results from an inherited deficiency of alpha-1 antitrypsin. Further, cystic fibrosis is the second most common childhood onset inherited disorder in the United States.
Transplantable alveolar epithelial type II cells may also one day be helpful in the treatment of other lung diseases including chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, claiming the lives of 122,283 Americans in 2003, and asthma, Wetsel said.
Still years away from their use in regenerative medicine, Wetsel said the next step involves research trials with mice.
Other IMM investigators participating in the study included David L. Haviland, Ph.D., assistant professor in the Center for Immunology and Autoimmune Diseases, and Eva Zsigmond, Ph.D., assistant professor and associate director of the IMM’s Laboratory for Developmental Biology.
Funding for the study of the NIH-approved human embryonic stem cell line was provided by Houston philanthropists Clive and Nancy Runnells.
The most comprehensive academic health center in the Southwest, the UT Health Science Center at Houston is home to six schools devoted to medicine, nursing, public health, dentistry, health informatics and graduate studies in biomedical science. In addition to the IMM, other components are the UT Harris County Psychiatric Center and the Mental Sciences Institute. The UT Health Science Center at Houston, founded in 1972, is part of the University of Texas System. It is a state-supported health institution whose state funding is supplemented by competitive research grants, patient fees and private philanthropy.
Rob Cahill | EurekAlert!
Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen
New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
15.08.2018 | Physics and Astronomy
15.08.2018 | Earth Sciences
15.08.2018 | Physics and Astronomy