U.S. scientists create artificial lungs, of sorts
Thursday, June 24, 2010
Lung Transplantation By Julie Steenhuysen
CHICAGO (Reuters) - Two U.S. teams have taken major strides in developing lab-engineered lung tissue that could be used for future transplants or testing the effects of new drugs.
In one study, a team at Yale University in Connecticut implanted engineered lung tissue into rats that worked like the real thing, helping the animals breathe and supplying their blood with fresh oxygen.
In another, a team at Harvard University in Massachusetts developed a tiny lung device from human tissue and synthetic materials to test for environmental toxins or see if new drugs work.
Both studies published on Thursday highlight advances in tissue engineering, in which researchers combine synthetic materials and human cells to work like natural organs.
"This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans," said Dr. Laura Niklason of Yale, whose study appears in the journal Science.
Niklason's team stripped away cells from rat lung that could cause organ rejection, and used the remaining shell as their starting point.
They infused this tissue with lung-specific stem cells and placed them in a bioreactor -- a kind of incubator built to resemble fetal-like conditions.
"What we found very much to our surprise was the cells generally landed in their correct anatomical location. We think that means the decellularized matrix has (postal) zip codes," Niklason said in a telephone interview.
When implanted into rats, the lung functioned much like a normal lung for up to two hours, Niklason said.
At first, "it was pretty close to perfect," she said.
But after a while, blood clots began to form, suggesting some of the cells that coat the blood vessels were sticky.Niklason said they plan to refine the process.
LUNG DEVICE
The team led by Donald Ingber, director of Harvard's Wyss Institute for Biologically Inspired Engineering, took an entirely different approach.
The idea was to develop a new way to study the lung that would be useful in drug development and might serve as a replacement for animal studies.
The device, about the size of a pea, mimics the function of air sacs called alveoli, which transfer oxygen through a thin membrane from the lung to the blood.
The device has three parts -- lung cells, a permeable membrane and tiny blood vessel or capillary cells. The whole thing is mounted on a microchip.
In one test, the team put E. coli bacteria on the lung side of the device, and sent white blood cells through the blood vessel side to mimic an immune system response.The white blood cells invaded the air sac chamber and destroyed the bacteria, Ingber said in a telephone interview.
The Harvard team has yet to show the device can actually exchange gases -- the essential function of the lung. But they are working on it. The team at Yale hopes to develop organs made from a person's own cells using embryonic-like stem cells called induced pluripotent stem cells or iPS cells.
"Ultimately, I would love to be able to generate a lung that could be implanted so we don't have to do lung transplants," Niklason said.
click for more info on this lung device
Tuesday, August 31, 2010
Artificial lungs grown in lab
Artificial lungs grown in lab
Lung-on-a-chip mircodevice light up by fluorescent dyes.
SYDNEY: In two breakthrough studies, American scientists have built a lung on a chip and successfully grown and transplanted a rat lung.
The research could help people who suffer from various lung diseases, which are often fatal due to the shortage of lung donors.
"This work represents an initial step towards the goal of creating fully functional lungs in the laboratory," said biomedical engineer Thomas Peterson from Yale University, New Haven.
How to grow a lung
Until now, scientists have been able to grow tissue, such as skin and cartilage, in a lab and transplant it into a patient. But complex organs such as lungs have remained out of their grasp.
But Peterson and his colleagues report this week that they have grown a rat lung in a lab and successfully transplanted them into rats. They published their study in the journal Science.
The left lung of a rat was 'decellularised' - that is, it was stripped of all its cells, leaving behind the basic scaffolding of the organ: its blood vessels. The researchers then introduced to the scaffold some stem cells from the rat that would receive the transplant. 20 to 25 years for human transplants
Once grown and transplanted, "the engineered lungs allowed oxygen to enter the bloodstream." The lung also removed carbon dioxide, though not as effectively as a natural lung.
But it will be "20-25 years before this approach can be attempted in human patients," Peterson said.
Biologist Miranda Grounds, at the University of Western Australia, who was not involved in the study, says that while the study has "demonstrated the principle", she cautions that it "would be exceedingly difficult to scale up to human applications."
Build a tiny model replica
In another study published in Science, Donald Ingber of the Wyss Institute for Biologically Inspired Engineering in Boston, and his colleagues scaled the lung down in size to what they refer to as a "organ-on-a-chip".
At approximately the size of an Australian 10 cent piece, the device mimics the human lung.
artificial-lungs-grown-lab at cosmos magazine click for more info
Friday, 25 June 2010by Emma Bastian
Cosmos Online
Lung-on-a-chip mircodevice light up by fluorescent dyes.
SYDNEY: In two breakthrough studies, American scientists have built a lung on a chip and successfully grown and transplanted a rat lung.
The research could help people who suffer from various lung diseases, which are often fatal due to the shortage of lung donors.
"This work represents an initial step towards the goal of creating fully functional lungs in the laboratory," said biomedical engineer Thomas Peterson from Yale University, New Haven.
How to grow a lung
Until now, scientists have been able to grow tissue, such as skin and cartilage, in a lab and transplant it into a patient. But complex organs such as lungs have remained out of their grasp.
But Peterson and his colleagues report this week that they have grown a rat lung in a lab and successfully transplanted them into rats. They published their study in the journal Science.
The left lung of a rat was 'decellularised' - that is, it was stripped of all its cells, leaving behind the basic scaffolding of the organ: its blood vessels. The researchers then introduced to the scaffold some stem cells from the rat that would receive the transplant. 20 to 25 years for human transplants
Once grown and transplanted, "the engineered lungs allowed oxygen to enter the bloodstream." The lung also removed carbon dioxide, though not as effectively as a natural lung.
But it will be "20-25 years before this approach can be attempted in human patients," Peterson said.
Biologist Miranda Grounds, at the University of Western Australia, who was not involved in the study, says that while the study has "demonstrated the principle", she cautions that it "would be exceedingly difficult to scale up to human applications."
Build a tiny model replica
In another study published in Science, Donald Ingber of the Wyss Institute for Biologically Inspired Engineering in Boston, and his colleagues scaled the lung down in size to what they refer to as a "organ-on-a-chip".
At approximately the size of an Australian 10 cent piece, the device mimics the human lung.
artificial-lungs-grown-lab at cosmos magazine click for more info
Friday, 25 June 2010by Emma Bastian
Cosmos Online
Monday, August 30, 2010
Scientists create replacement lungs
Scientists create replacement lungs
US scientists have reported important progress towards building new human lungs by successfully implanting lab-cultivated cells into a rat's lungs, and by creating an artificial device on a microchip that mimics the human lung.
Yale University researchers managed to create lungs that worked from 45 to 120 minutes by using laboratory-cultivated cells and implanted them into rats, a scientific first.
Separately, researchers with the Wyss Institute at Harvard University, Harvard Medical School and Children's Hospital Boston created a device that acts like a human lung using blood vessel cells. It is about the size of a rubber eraser.
The artificial lung can be used to test the effects of new medicine and toxins on human lungs, said Wyss Institute director Donald Ingber and the study's main author.
The mini lung-on-a-chip "merges a number of technologies in an innovative way," said MIT Institute professor Robert Langer on Thursday.
"I think it should be useful in testing the safety of different substances on the lung and I can also imagine other related applications, such as in research into how the lung functions," he added.
Both research studies appear in the June 25 edition of the journal Science.
For the first study, researchers took adult rat lungs and removed their existing cellular components.
They preserved the matrix and branching structures of the airways and vascular system, which they later used to grow new lung cells.
"When implanted into rats for short intervals of time (45-120 minutes), the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs," the researchers said.
"We succeeded in engineering an implantable lung in our rat model that could efficiently exchange oxygen and carbon dioxide, and could oxygenate hemoglobin in the blood," said lead author Laura Niklason from Yale University.
"This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans," she said.
Niklason however warned that it will take years of research with adult stem cells to see if lungs can be regenerated in vitro, successfully implanted into patients, and made sure they function properly.
The Yale team found that the engineered lungs were similar to those of native tissues, and properly exchanged oxygen and carbon dioxide when implanted.
Some 400,000 people die annually in the United States of lung diseases.
Lung tissue is especially difficult to regenerate because it rarely repairs beyond the microscopic level, researchers said. "The only current way to replace damaged adult lung tissue is to perform lung transplantation, which is highly susceptible to organ rejection and infection and achieves only 10 per cent to 20 per cent survival at 10 years," the Yale researchers said.
click to see more scientists grow replacement parts lungs
US scientists have reported important progress towards building new human lungs by successfully implanting lab-cultivated cells into a rat's lungs, and by creating an artificial device on a microchip that mimics the human lung.
Yale University researchers managed to create lungs that worked from 45 to 120 minutes by using laboratory-cultivated cells and implanted them into rats, a scientific first.
Separately, researchers with the Wyss Institute at Harvard University, Harvard Medical School and Children's Hospital Boston created a device that acts like a human lung using blood vessel cells. It is about the size of a rubber eraser.
The artificial lung can be used to test the effects of new medicine and toxins on human lungs, said Wyss Institute director Donald Ingber and the study's main author.
The mini lung-on-a-chip "merges a number of technologies in an innovative way," said MIT Institute professor Robert Langer on Thursday.
"I think it should be useful in testing the safety of different substances on the lung and I can also imagine other related applications, such as in research into how the lung functions," he added.
Both research studies appear in the June 25 edition of the journal Science.
For the first study, researchers took adult rat lungs and removed their existing cellular components.
They preserved the matrix and branching structures of the airways and vascular system, which they later used to grow new lung cells.
"When implanted into rats for short intervals of time (45-120 minutes), the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs," the researchers said.
"We succeeded in engineering an implantable lung in our rat model that could efficiently exchange oxygen and carbon dioxide, and could oxygenate hemoglobin in the blood," said lead author Laura Niklason from Yale University.
"This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans," she said.
Niklason however warned that it will take years of research with adult stem cells to see if lungs can be regenerated in vitro, successfully implanted into patients, and made sure they function properly.
The Yale team found that the engineered lungs were similar to those of native tissues, and properly exchanged oxygen and carbon dioxide when implanted.
Some 400,000 people die annually in the United States of lung diseases.
Lung tissue is especially difficult to regenerate because it rarely repairs beyond the microscopic level, researchers said. "The only current way to replace damaged adult lung tissue is to perform lung transplantation, which is highly susceptible to organ rejection and infection and achieves only 10 per cent to 20 per cent survival at 10 years," the Yale researchers said.
click to see more scientists grow replacement parts lungs
Update on Work on Artificial Lung Prototypes
Update on Work on Artificial Lung Prototypes
The McGowan Institute scientists are developing improved artificial lungs. Brack G. Hattler, MD, PhD (bottom), Professor of Surgery and Executive Director of the Medical Devices Laboratory at the University of Pittsburgh, and William J. Federspiel, PhD (top), the University’s William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering, and Director of the Medical Devices Laboratory, currently are conducting laboratory research that is tackling fundamental problems associated with making artificial lungs more efficient and biocompatible, and is developing next generation artificial lungs or blood oxygenators.
The purpose of an artificial lung is to help lung-failure patients survive the tenuous bridge of time between loss of respiratory function and a lung transplant, and to allow a patient whose lungs have undergone trauma, like severe smoke inhalation, to rest and heal. Artificial lungs are small and portable, and are designed to allow patients to remain mobile and therefore stronger for surgery. In healthy lungs, blood vessels absorb oxygen from the blood that's pumped in from the heart, then release carbon dioxide through exhalation. An artificial lung basically imitates the way a normal lung works.
Researchers in Pittsburgh who are developing and testing prototypes believe artificial lung clinical trials in humans, similar to studies already underway in Canada and Europe, may begin as early as this spring.
"We are doing extensive work with the Department of Defense," says Dr. Hattler. "They are very interested in support of soldiers in combat." He expects human trials this spring for his group's external device, the Hemolung.
The Hemolung consists of a small cylindrical oxygenator that is approximately 4 inches in diameter. A cylindrical bundle of micro-porous hollow fiber membranes woven into a mat is wrapped in multiple layers around a central core. Oxygen flows through the hollow fiber membranes, while blood is circulated though the hollow fiber bundle. The core is spun at approximately 1000 RPM, dramatically enhancing gas exchange, as well as serving as a pump to move the blood through the external circuit. The 6-month clinical trial could begin early in 2008 on the Hemolung. Hope is that the FDA will approve it quickly, for patient use by the end of 2008.
see more info on this hemolung
The McGowan Institute scientists are developing improved artificial lungs. Brack G. Hattler, MD, PhD (bottom), Professor of Surgery and Executive Director of the Medical Devices Laboratory at the University of Pittsburgh, and William J. Federspiel, PhD (top), the University’s William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering, and Director of the Medical Devices Laboratory, currently are conducting laboratory research that is tackling fundamental problems associated with making artificial lungs more efficient and biocompatible, and is developing next generation artificial lungs or blood oxygenators.
The purpose of an artificial lung is to help lung-failure patients survive the tenuous bridge of time between loss of respiratory function and a lung transplant, and to allow a patient whose lungs have undergone trauma, like severe smoke inhalation, to rest and heal. Artificial lungs are small and portable, and are designed to allow patients to remain mobile and therefore stronger for surgery. In healthy lungs, blood vessels absorb oxygen from the blood that's pumped in from the heart, then release carbon dioxide through exhalation. An artificial lung basically imitates the way a normal lung works.
Researchers in Pittsburgh who are developing and testing prototypes believe artificial lung clinical trials in humans, similar to studies already underway in Canada and Europe, may begin as early as this spring.
"We are doing extensive work with the Department of Defense," says Dr. Hattler. "They are very interested in support of soldiers in combat." He expects human trials this spring for his group's external device, the Hemolung.
The Hemolung consists of a small cylindrical oxygenator that is approximately 4 inches in diameter. A cylindrical bundle of micro-porous hollow fiber membranes woven into a mat is wrapped in multiple layers around a central core. Oxygen flows through the hollow fiber membranes, while blood is circulated though the hollow fiber bundle. The core is spun at approximately 1000 RPM, dramatically enhancing gas exchange, as well as serving as a pump to move the blood through the external circuit. The 6-month clinical trial could begin early in 2008 on the Hemolung. Hope is that the FDA will approve it quickly, for patient use by the end of 2008.
see more info on this hemolung
Tissue-Engineered Lungs for in Vivo Implantation
Tissue-Engineered Lungs for in Vivo Implantation
Thomas H. Petersen,1,2 Elizabeth A. Calle,1 Liping Zhao,3 Eun Jung Lee,3 Liqiong Gui,3 MichaSam B. Raredon,1 Kseniya Gavrilov,4 Tai Yi,5 Zhen W. Zhuang,6 Christopher Breuer,5 Erica Herzog,6 Laura E. Niklason1,3,*
Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 min), the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
1 Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
2 Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3 Department of Anesthesia, Yale University, New Haven, CT 06520, USA.
4 Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
5 Department of Surgery, Yale University, New Haven, CT 06520, USA.
6 Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
* To whom correspondence should be addressed. Email: laura.niklason@yale.edu
see more info at sciencemag.org
Thomas H. Petersen,1,2 Elizabeth A. Calle,1 Liping Zhao,3 Eun Jung Lee,3 Liqiong Gui,3 MichaSam B. Raredon,1 Kseniya Gavrilov,4 Tai Yi,5 Zhen W. Zhuang,6 Christopher Breuer,5 Erica Herzog,6 Laura E. Niklason1,3,*
Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 min), the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
1 Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
2 Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3 Department of Anesthesia, Yale University, New Haven, CT 06520, USA.
4 Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
5 Department of Surgery, Yale University, New Haven, CT 06520, USA.
6 Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
* To whom correspondence should be addressed. Email: laura.niklason@yale.edu
see more info at sciencemag.org
Regeneration and orthotopic transplantation of a bioartificial lung
Regeneration and orthotopic transplantation of a bioartificial lung
Harald C Ott1, Ben Clippinger1, Claudius Conrad1, Christian Schuetz1, Irina Pomerantseva1, Laertis Ikonomou2, Darrell Kotton2 & Joseph P Vacanti1
Abstract
About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.
http://www.nature.com/nm/journal/v16/n8/abs/nm.2193.html
Harald C Ott1, Ben Clippinger1, Claudius Conrad1, Christian Schuetz1, Irina Pomerantseva1, Laertis Ikonomou2, Darrell Kotton2 & Joseph P Vacanti1
Abstract
About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.
http://www.nature.com/nm/journal/v16/n8/abs/nm.2193.html
Scientists seek to grow new lungs from stem cells
Scientists seek to grow new lungs from stem cells
For someone with a severe, incurable lung disorder such as cystic fibrosis or chronic obstructive pulmonary disease, a lung transplant may be the only chance for survival. Unfortunately, it’s often not a very good chance. Matching donor lungs are rare, and many would-be recipients die waiting for the transplants that could save their lives.
Such deaths could be prevented if it were possible to use stem cells to grow new lungs or lung tissue. Specialists in the emerging field of tissue engineering have been hard at work on this for years. But they’ve been frustrated by the problem of coaxing undifferentiated stem cells to develop into the specific cell types that populate different locations in the lung.
Now, researchers from UTMB have demonstrated a potentially revolutionary solution to this problem. As they describe in an article published electronically ahead of print by the journal Tissue Engineering Part A, they seeded mouse embryonic stem cells into “acellular” rat lungs — organs whose original cells had been destroyed by repeated cycles of freezing and thawing and exposure to detergent.
The result: empty lung-shaped scaffolds of structural proteins on which the mouse stem cells thrived and differentiated into new cells appropriate to their specific locations.
“In terms of different cell types, the lung is probably the most complex of all organs — the cells near the entrance are very different from those deep in the lung,” said Dr. Joaquin Cortiella, one of the article’s lead authors. “Our natural matrix generated the same pattern, with tracheal cells only in the trachea, alveoli-like cells in the alveoli, pneumocytes only in the distal lung, and definite transition zones between the bronchi and the alveoli.”
Such “site-specific” cell development has never been seen before in a natural matrix, said Dr. Joan Nichols, another of the paper’s lead authors. The complexity gives the researchers hope that the concept could be scaled up to produce replacement tissues for humans — or used to create models to test therapies and diagnostic techniques for a variety of lung diseases.
“If we can make a good lung for people, we can also make a good model for injury,” Nichols said. “We can create a fibrotic lung, or an emphysematous lung, and evaluate what’s happening with those, what the cells are doing, how well stem cell or other therapy works. We can see what happens in pneumonia, or what happens when you’ve got a hemorrhagic fever, or tuberculosis, or hantavirus — all the agents that target the lung and cause damage in the lung.”
The researchers have already begun work on large-scale experiments, “decellularizing” pig lungs with an eye toward using them to produce larger samples of lung tissue that could lead to applications in humans. They’re also taking on the challenge of vascularization — stimulating the growth of blood vessels that will enable the engineered tissues to survive outside the special bioreactors that the researchers now use to keep them alive by bathing them in a life-sustaining cocktail of nutrients and oxygen.
“People ask us why we’re doing the lung, because it’s so hard,” Cortiella said. “But the potential is so great, and the technology is here. It’s going to take time, but I think we’re going to create a system that works.”
by Jim Kelly
see the article on lungs from stem cells at utmb.edu
For someone with a severe, incurable lung disorder such as cystic fibrosis or chronic obstructive pulmonary disease, a lung transplant may be the only chance for survival. Unfortunately, it’s often not a very good chance. Matching donor lungs are rare, and many would-be recipients die waiting for the transplants that could save their lives.
Such deaths could be prevented if it were possible to use stem cells to grow new lungs or lung tissue. Specialists in the emerging field of tissue engineering have been hard at work on this for years. But they’ve been frustrated by the problem of coaxing undifferentiated stem cells to develop into the specific cell types that populate different locations in the lung.
Now, researchers from UTMB have demonstrated a potentially revolutionary solution to this problem. As they describe in an article published electronically ahead of print by the journal Tissue Engineering Part A, they seeded mouse embryonic stem cells into “acellular” rat lungs — organs whose original cells had been destroyed by repeated cycles of freezing and thawing and exposure to detergent.
The result: empty lung-shaped scaffolds of structural proteins on which the mouse stem cells thrived and differentiated into new cells appropriate to their specific locations.
“In terms of different cell types, the lung is probably the most complex of all organs — the cells near the entrance are very different from those deep in the lung,” said Dr. Joaquin Cortiella, one of the article’s lead authors. “Our natural matrix generated the same pattern, with tracheal cells only in the trachea, alveoli-like cells in the alveoli, pneumocytes only in the distal lung, and definite transition zones between the bronchi and the alveoli.”
Such “site-specific” cell development has never been seen before in a natural matrix, said Dr. Joan Nichols, another of the paper’s lead authors. The complexity gives the researchers hope that the concept could be scaled up to produce replacement tissues for humans — or used to create models to test therapies and diagnostic techniques for a variety of lung diseases.
“If we can make a good lung for people, we can also make a good model for injury,” Nichols said. “We can create a fibrotic lung, or an emphysematous lung, and evaluate what’s happening with those, what the cells are doing, how well stem cell or other therapy works. We can see what happens in pneumonia, or what happens when you’ve got a hemorrhagic fever, or tuberculosis, or hantavirus — all the agents that target the lung and cause damage in the lung.”
The researchers have already begun work on large-scale experiments, “decellularizing” pig lungs with an eye toward using them to produce larger samples of lung tissue that could lead to applications in humans. They’re also taking on the challenge of vascularization — stimulating the growth of blood vessels that will enable the engineered tissues to survive outside the special bioreactors that the researchers now use to keep them alive by bathing them in a life-sustaining cocktail of nutrients and oxygen.
“People ask us why we’re doing the lung, because it’s so hard,” Cortiella said. “But the potential is so great, and the technology is here. It’s going to take time, but I think we’re going to create a system that works.”
by Jim Kelly
see the article on lungs from stem cells at utmb.edu
Sunday, August 29, 2010
Artificial lung tissue developed for premies
Artificial lung tissue developed for premies
Pre-term babies have several obstacles to overcome, and one of the most challenging is pulmonary hypoplasia. The condition involves underdeveloped lungs and a decreased number of alveoli, the primary sites of gas exchange.
In addition to the low number, the alveoli are also deficient in the surfactant produced by the epithelial cells, leading to a near-blockage to the flow of gas.
Although there have been various state-of-the-art treatments for pulmonary hypoplasia, later in life, infants can still suffer from pulmonary hypertension, hyaline membrane disease and acute respiratory distress syndrome.
It was clear to the laboratory of Fizan Abdullah that the solution to this neonatal condition was in regenerative medicine. As a result, this Biomedical Engineering lab, combined with the Pediatric Surgery and Mechanical Engineering departments, worked to create an artificial alveolar-capillary membrane that could one day put an end to a rare but life-threatening condition.
Before publishing their results in the Journal of Pediatric Surgery, the lab created two generations of the membrane.
Both membrane types were created to physiologically-relevant scales. Each microdevice could support several microfluidic cell cultures. These two membrane-like microdevices closely mimic the real tissue found at the the alveolus-capillary interface, but differ in the number of stages used.
"Due the complexity of the system, we decided to take it as a progressive series by adding a new parameter every generation. The first-generation devices were used to test the pulmonary cell types to various fluid shear regimes and also to come up with the range of flow velocities sustainable by the different cell types," Divya Nalayanda, a Ph.D. candidate at the School of Medicine, said of their first model.
"We observed that the different cell types could resist fluid shear to different levels, with the endothelial cell types capable of withstanding high fluid shear than alveolar cells."
Endothelial cells are one of the three types of cells that predominate the alveolus surface; the other two are alveolar and mesenchymal. One of the main differences between the first and second microdevices was that the first one had only a single-layer microfluidic chip.
The second generation device was multi-layered. "We added the air-interface to mimic the lung environment wherein the alveolar cells are constantly exposed to air on its apical side."
The cells used for culture included A549 human alveolar epithelial cells, HMEC-1 human microvascular endothelial cells, and fetal pulmonary cells harvested from Swiss-Webster mice. Each cell type was monitored under the a microscope.
The viability of each cell line was measured using a live-dead assay, which is a two-color fluorescence assay that uses a standard curve to determine the number of living and dead cells.
The starting cell lines were the A549 and HMEC-1, both of which were used to make sure that the microfluidic chips could sustain cells. They provided a simple system, allowing the lab members to understand the isolated effects of fluid shear and air exposure on a single cell type.
"[We] followed with a mixed population of fetal pulmonary cells since our lab is interested in studying the initial effects of air-exposure to pre-natal alveolar cells," Nalayanda said.
Currently, the lab is continuing to study the fetal cells in various conditions. "We have only had the preliminary results of fluid shear effects on them. Some of the initial observations indicated other parameters critically affecting the results such as cell passage number, percent of alveolar cells in the mixed population, seeding density, and surface coating."
Nalayanda also mentioned the need to incorporate surface tension in their study. "In vivo, the alveolar epithelial cells are known to produce various surfactant proteins to reduce the surface tension of the alveolar gas-exchange surface."
As a result, the lab is testing the cumulative effect of all of the surfactant proteins in reducing the surface-tension at the site of gas exchange, since one of the most damaging symptoms of pulmonary hypoplasia is the increased surface tension between the capillary and alveolus due to the decreased production of surfactant.
Nalayanda and the rest of the lab still have a ways to go before their cutting-edge engineering feat can be implemented in medicine. They are planning to continue their research by creating yet another generation of microdevices.
"[We] are planning to progress to a co-culture system with a dynamic air-liquid interface that could be used as a high-throughput system to perform pulmonary drug permeability studies and cell response," Nalayanda said.
This could ensure that the microdevices are agreeable to in vivo conditions, progressing them past the biomimetic model stage to the regenerative medicine that could save 2800 lives a year.
ScienceTech Artificial.Lung. Tissue Developed For Premies
By: Aleena Lakhanpal
Posted: 2/11/10
Pre-term babies have several obstacles to overcome, and one of the most challenging is pulmonary hypoplasia. The condition involves underdeveloped lungs and a decreased number of alveoli, the primary sites of gas exchange.
In addition to the low number, the alveoli are also deficient in the surfactant produced by the epithelial cells, leading to a near-blockage to the flow of gas.
Although there have been various state-of-the-art treatments for pulmonary hypoplasia, later in life, infants can still suffer from pulmonary hypertension, hyaline membrane disease and acute respiratory distress syndrome.
It was clear to the laboratory of Fizan Abdullah that the solution to this neonatal condition was in regenerative medicine. As a result, this Biomedical Engineering lab, combined with the Pediatric Surgery and Mechanical Engineering departments, worked to create an artificial alveolar-capillary membrane that could one day put an end to a rare but life-threatening condition.
Before publishing their results in the Journal of Pediatric Surgery, the lab created two generations of the membrane.
Both membrane types were created to physiologically-relevant scales. Each microdevice could support several microfluidic cell cultures. These two membrane-like microdevices closely mimic the real tissue found at the the alveolus-capillary interface, but differ in the number of stages used.
"Due the complexity of the system, we decided to take it as a progressive series by adding a new parameter every generation. The first-generation devices were used to test the pulmonary cell types to various fluid shear regimes and also to come up with the range of flow velocities sustainable by the different cell types," Divya Nalayanda, a Ph.D. candidate at the School of Medicine, said of their first model.
"We observed that the different cell types could resist fluid shear to different levels, with the endothelial cell types capable of withstanding high fluid shear than alveolar cells."
Endothelial cells are one of the three types of cells that predominate the alveolus surface; the other two are alveolar and mesenchymal. One of the main differences between the first and second microdevices was that the first one had only a single-layer microfluidic chip.
The second generation device was multi-layered. "We added the air-interface to mimic the lung environment wherein the alveolar cells are constantly exposed to air on its apical side."
The cells used for culture included A549 human alveolar epithelial cells, HMEC-1 human microvascular endothelial cells, and fetal pulmonary cells harvested from Swiss-Webster mice. Each cell type was monitored under the a microscope.
The viability of each cell line was measured using a live-dead assay, which is a two-color fluorescence assay that uses a standard curve to determine the number of living and dead cells.
The starting cell lines were the A549 and HMEC-1, both of which were used to make sure that the microfluidic chips could sustain cells. They provided a simple system, allowing the lab members to understand the isolated effects of fluid shear and air exposure on a single cell type.
"[We] followed with a mixed population of fetal pulmonary cells since our lab is interested in studying the initial effects of air-exposure to pre-natal alveolar cells," Nalayanda said.
Currently, the lab is continuing to study the fetal cells in various conditions. "We have only had the preliminary results of fluid shear effects on them. Some of the initial observations indicated other parameters critically affecting the results such as cell passage number, percent of alveolar cells in the mixed population, seeding density, and surface coating."
Nalayanda also mentioned the need to incorporate surface tension in their study. "In vivo, the alveolar epithelial cells are known to produce various surfactant proteins to reduce the surface tension of the alveolar gas-exchange surface."
As a result, the lab is testing the cumulative effect of all of the surfactant proteins in reducing the surface-tension at the site of gas exchange, since one of the most damaging symptoms of pulmonary hypoplasia is the increased surface tension between the capillary and alveolus due to the decreased production of surfactant.
Nalayanda and the rest of the lab still have a ways to go before their cutting-edge engineering feat can be implemented in medicine. They are planning to continue their research by creating yet another generation of microdevices.
"[We] are planning to progress to a co-culture system with a dynamic air-liquid interface that could be used as a high-throughput system to perform pulmonary drug permeability studies and cell response," Nalayanda said.
This could ensure that the microdevices are agreeable to in vivo conditions, progressing them past the biomimetic model stage to the regenerative medicine that could save 2800 lives a year.
ScienceTech Artificial.Lung. Tissue Developed For Premies
By: Aleena Lakhanpal
Posted: 2/11/10
Mass. General researchers build artificial rat lung
Mass. General researchers build artificial rat lung
A team led by Massachusetts General Hospital researchers has built a functioning artificial rat lung and successfully transplanted it into living rats, where it functioned for six hours.
The work, published online today in the journal Nature Medicine, follows two recent scientific reports of success in replicating lung tissue, including work by Yale researchers that used the same technique.
In the new paper, researchers took a lung from a rat and used it as a scaffold for building new lung. They carefully washed away all the cells, and then reseeded the matrix left behind with cells from a fetal rat lung. They transplanted the lung into rats and saw the lung function for up to six hours.
“Our experiment shows that the rat is able to breathe with that lung, using its own muscles,” said Dr. Harald Ott, a surgical resident at Mass. General.
About 2,000 patients in the United States are awaiting a lung transplant, and 50 million people worldwide live with end-stage lung disease, making the quest to create an artificial lung ever more urgent. Ott said that next steps include finding a way to make precursor cells that give rise to lung cells from a patient’s own cells and other technical hurdles involved in scaling up such techniques from a rat to a human lung.
His team’s paper, in tandem with the Yale researchers' paper in which the rat lung functioned for up to two hours, are important because they both were successful.
“It validates this approach; it shows that I’m not crazy,” Ott said. “Which is important, because there’s a lot of enthusiasm around organ engineering, and lots of optimistic statements flying around.”
from Boston Mass General hospital
Comments (0) Posted by Carolyn Y. Johnson July 13, 2010
A team led by Massachusetts General Hospital researchers has built a functioning artificial rat lung and successfully transplanted it into living rats, where it functioned for six hours.
The work, published online today in the journal Nature Medicine, follows two recent scientific reports of success in replicating lung tissue, including work by Yale researchers that used the same technique.
In the new paper, researchers took a lung from a rat and used it as a scaffold for building new lung. They carefully washed away all the cells, and then reseeded the matrix left behind with cells from a fetal rat lung. They transplanted the lung into rats and saw the lung function for up to six hours.
“Our experiment shows that the rat is able to breathe with that lung, using its own muscles,” said Dr. Harald Ott, a surgical resident at Mass. General.
About 2,000 patients in the United States are awaiting a lung transplant, and 50 million people worldwide live with end-stage lung disease, making the quest to create an artificial lung ever more urgent. Ott said that next steps include finding a way to make precursor cells that give rise to lung cells from a patient’s own cells and other technical hurdles involved in scaling up such techniques from a rat to a human lung.
His team’s paper, in tandem with the Yale researchers' paper in which the rat lung functioned for up to two hours, are important because they both were successful.
“It validates this approach; it shows that I’m not crazy,” Ott said. “Which is important, because there’s a lot of enthusiasm around organ engineering, and lots of optimistic statements flying around.”
from Boston Mass General hospital
Comments (0) Posted by Carolyn Y. Johnson July 13, 2010
The Human Need for the Haemair Device
The Human Need for the Haemair Device
Lung disease is a major cause of premature death. Millions of people die every year who, apart from lung disease, could lead healthy lives. People are dying both of acute conditions and of chronic conditions. Acute conditions arise typically from viral or bacterial infection and lead to rapid deterioration of lung function. Chronic conditions continue throughout the patient's life, often resulting in a slow, but inexorable, decline in lung function. Lung disease is an increasing problem, and urgent means are needed to improve recovery and provide longer lives of better quality. We discuss each class of disease separately:
Acute Respiratory Infection kills almost 4 million people every year (WHO figures). The number of people who die is only a fraction of the number who contract ARI. Of those who do not die, a significant number have permanently reduced lung function.
Chronic Lung Disease kills a similar number of people. There are a wide range of chronic conditions including Emphysema, Cystic Fibrosis and Asthma. For steadily deteriorating conditions, the only treatment is lung transplantation. However, only a very small proportion of chronic lung disease sufferers are offered transplantation.
For example, there are very few transplants for over-50's, but most emphysema sufferers are over 50. In the UK, about 3,000 people die from emphysema every year; almost none are offered transplant. Taking Europe and North America together, there are approximately ten times that number of emphysema deaths. Emphysema is only one of dozens of chronic lung conditions.
Of those who are put on transplant lists, the prospects are not good. Thus, in Europe and North America, there are about 10,000 people on lung-transplant waiting lists. Each year, about 5,000 join and 5,000 leave the lists. Of those leaving, about 2,500 die waiting, about 750 die during or soon after transplant, and about 1,750 live healthy lives with their new lungs.
Our device is designed to replace lung function entirely. It should give a higher recovery rate for Acute Respiratory Infection, and reduced lung damage for those who do recover. It should permit chronic sufferers to conduct active lives, outside Intensive Care units (for example, at home). It can act as a bridge to lung transplant, giving healthier transplant patients with better recovery prospects. In the long run, we hope to provide a full alternative to lung transplant. Such an alternative gives hope for hundreds of thousands currently denied transplant. Furthermore, it gives the possibility for "on demand transplantation", which may be the only hope for conditions ranging from chemical and biological weapons victims to lung cancer sufferers.
"Haemair Limited has a mission to reduce Acute deaths, improve the lives of Chronic sufferers and to provide an alternative to lung transplantation."
Haemair Ltd.
Lung disease is a major cause of premature death. Millions of people die every year who, apart from lung disease, could lead healthy lives. People are dying both of acute conditions and of chronic conditions. Acute conditions arise typically from viral or bacterial infection and lead to rapid deterioration of lung function. Chronic conditions continue throughout the patient's life, often resulting in a slow, but inexorable, decline in lung function. Lung disease is an increasing problem, and urgent means are needed to improve recovery and provide longer lives of better quality. We discuss each class of disease separately:
Acute Respiratory Infection kills almost 4 million people every year (WHO figures). The number of people who die is only a fraction of the number who contract ARI. Of those who do not die, a significant number have permanently reduced lung function.
Chronic Lung Disease kills a similar number of people. There are a wide range of chronic conditions including Emphysema, Cystic Fibrosis and Asthma. For steadily deteriorating conditions, the only treatment is lung transplantation. However, only a very small proportion of chronic lung disease sufferers are offered transplantation.
For example, there are very few transplants for over-50's, but most emphysema sufferers are over 50. In the UK, about 3,000 people die from emphysema every year; almost none are offered transplant. Taking Europe and North America together, there are approximately ten times that number of emphysema deaths. Emphysema is only one of dozens of chronic lung conditions.
Of those who are put on transplant lists, the prospects are not good. Thus, in Europe and North America, there are about 10,000 people on lung-transplant waiting lists. Each year, about 5,000 join and 5,000 leave the lists. Of those leaving, about 2,500 die waiting, about 750 die during or soon after transplant, and about 1,750 live healthy lives with their new lungs.
Our device is designed to replace lung function entirely. It should give a higher recovery rate for Acute Respiratory Infection, and reduced lung damage for those who do recover. It should permit chronic sufferers to conduct active lives, outside Intensive Care units (for example, at home). It can act as a bridge to lung transplant, giving healthier transplant patients with better recovery prospects. In the long run, we hope to provide a full alternative to lung transplant. Such an alternative gives hope for hundreds of thousands currently denied transplant. Furthermore, it gives the possibility for "on demand transplantation", which may be the only hope for conditions ranging from chemical and biological weapons victims to lung cancer sufferers.
"Haemair Limited has a mission to reduce Acute deaths, improve the lives of Chronic sufferers and to provide an alternative to lung transplantation."
Haemair Ltd.
Haemair respiratory aid and prosthetic lung
The Haemair respiratory aid and prosthetic lung.
The unique feature of the Haemair approach is that it is aimed at conscious mobile patients. To this end, we match oxygen and carbon dioxide mass transfer rates to the respiratory demand of the patient. Furthermore, we employ a flow of natural air to provide oxygen and remove carbon dioxide.
There are three main variants of our device. The simplest to employ consists of a mass exchanger, as illustrated in figure 2. It takes deoxygenated blood, extracted from a main vein, removes carbon dioxide, replaces it with oxygen, and returns the oxygenated blood to the body. The second variant places the mass exchanger within the body to eliminate the hazard of taking a significant blood flow outside the body. The final version is a prosthetic lung, as illustrated in figure 3.
In all three variants, mass transfer is controlled so that performance mimics that of natural lungs. In this way, the natural respiratory control mechanism controls heart rate etc, and control is fully integrated with the natural respiratory system.
The external device will be deployed first. It is easily reversible and major parts are available for maintenance. The easy reversibility is important in treating emergency and acute cases for which the device might be needed for no more than hours or weeks. Once we have established that long maintenance-free operation is possible, we can move on to the intermediate device. The clinical procedure to “plumb” the device into the blood circulation system is more complex and maintenance is more difficult. However, the engineering is simpler. The only significant external item required is a small air pump, or fan. This device is more suited to patients who will need it for months – for example, as a bridge to transplant. It should enable patients to leave hospital and continue treatment at home. The final variant, a prosthetic lung, serves as an alternative to a lung transplant. This variant is illustrated in figure 3. It cannot be deployed until we have extensive favourable experience with the reversible devices. However, it offers hope to those currently excluded from transplant waiting lists – for example, most terminal emphysema sufferers.
For those interested in the technology, our published PCT Patent Application No. W02005/118025 is available. Details of subsequent applications can be provided against suitable signed confidentiality agreements. Please contact Haemair explaining your interest. We are pleased to share information with those who share our goal of improving the lives of sufferers from lung disease.
"Haemair Limited has a mission to reduce Acute deaths, improve the lives of Chronic sufferers and to provide an alternative to lung transplantation."
The unique feature of the Haemair approach is that it is aimed at conscious mobile patients. To this end, we match oxygen and carbon dioxide mass transfer rates to the respiratory demand of the patient. Furthermore, we employ a flow of natural air to provide oxygen and remove carbon dioxide.
There are three main variants of our device. The simplest to employ consists of a mass exchanger, as illustrated in figure 2. It takes deoxygenated blood, extracted from a main vein, removes carbon dioxide, replaces it with oxygen, and returns the oxygenated blood to the body. The second variant places the mass exchanger within the body to eliminate the hazard of taking a significant blood flow outside the body. The final version is a prosthetic lung, as illustrated in figure 3.
In all three variants, mass transfer is controlled so that performance mimics that of natural lungs. In this way, the natural respiratory control mechanism controls heart rate etc, and control is fully integrated with the natural respiratory system.
The external device will be deployed first. It is easily reversible and major parts are available for maintenance. The easy reversibility is important in treating emergency and acute cases for which the device might be needed for no more than hours or weeks. Once we have established that long maintenance-free operation is possible, we can move on to the intermediate device. The clinical procedure to “plumb” the device into the blood circulation system is more complex and maintenance is more difficult. However, the engineering is simpler. The only significant external item required is a small air pump, or fan. This device is more suited to patients who will need it for months – for example, as a bridge to transplant. It should enable patients to leave hospital and continue treatment at home. The final variant, a prosthetic lung, serves as an alternative to a lung transplant. This variant is illustrated in figure 3. It cannot be deployed until we have extensive favourable experience with the reversible devices. However, it offers hope to those currently excluded from transplant waiting lists – for example, most terminal emphysema sufferers.
For those interested in the technology, our published PCT Patent Application No. W02005/118025 is available. Details of subsequent applications can be provided against suitable signed confidentiality agreements. Please contact Haemair explaining your interest. We are pleased to share information with those who share our goal of improving the lives of sufferers from lung disease.
"Haemair Limited has a mission to reduce Acute deaths, improve the lives of Chronic sufferers and to provide an alternative to lung transplantation."
This website is designed to promote Artificial lungs
This website is designed to promote Artificial lungs.
Here's an image that I found on the web that provides the theme for this blog.
I personally suffer from severe emphysema , so I have an interest in this technology.
Hopefully this will be achieved in my lifetime,
Here's an image that I found on the web that provides the theme for this blog.
I personally suffer from severe emphysema , so I have an interest in this technology.
Hopefully this will be achieved in my lifetime,
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