How to build a lung

How to build a lung

Tissue engineering, a field that combines cell biology, engineering, and materials science to manufacture tissues – and more recently even whole organs – to replace those lost to injury or illness, must be one of the most exciting areas in modern medicine. Since the earliest reports about a mouse with a human ear growing on its back over a decade ago progress has been rapid, and last year we reported on how animal research enabled scientists to use a patient’s own stem cells to successfully replaced a trachea that suffered irreparable damage from tuberculosis.

Now science writer Ed Yong has written an excellent article on his Not Exactly Rocket Science blog about how a team of scientists at led by Laura Niklason Yale University are moving on from the trachea to a far more complex part of the respiratory system – the lung – and successfully transplanted it into rats. As Ed points out, this technology needs to be improved significantly before it can be attempted in humans, and further research in rats is underway to do just that. This work will take time, and as it progresses will almost certainly require studies in larger animals such as pigs whose lungs are closer to ours in size and structure than those of rats. Human trials are not expected for perhaps a decade or more.

Ed Yong was not the only one to note the importance of this research, the journal Science, in which the study was published (1), have included an interview with Laura Niklason in their latest podcast.


How to build a lung. Courtesy of Laura Niklason and Thomas Petersen.

Laura Niklason’s past record certainly gives cause for optimism. In 1999 they published a paper describing how they engineered arteries in vitro that supported blood flow when transplanted into pigs, an animal whose cardiovascular system is a valuable model for our own, and determined that a culture technique that mimics the pulsating arterial blood flow produced stronger and safer engineered arteries. Following a decade of refinement through in vitro tissue culture and animal research the artery is expected to enter human clinical trials next year.

This wasn’t the only exciting lung-related research to be published in Science this week. Scientists at Harvard University have used microfluidics to re-create the interface between the alveoli and capillaries (2) in the lung where exchange of oxygen and other gasses takes place. The response of this “Lab-on-a-chip” model to bacterial infection and inflammatory signals was similar to that seen in previous animal studies.

This technology represents huge advance over existing in vitro models of the lung; which, in addition to being a very promising research tool in its own right, has the potential to reduce the number of animals used in testing the effect of new drugs or toxins on lung function. Eventually an improved version, perhaps combined with chips that simulate other tissue types, might replace animal use in the evaluation of toxicity in the lung entirely, though that goal is still years of dedicated research away. Lab-on-a–chip technologies such as this that can integrate several cell types into a system that mimics real tissues in vivo are a great example of the 3Rs in action.


How to build a lung on a chip. Image courtesy of Huh D. et al. Science Volume 328 (5986), pages 1662 - 166 (2010)

One area the Harvard scientists were particularly interested in is using this lab-on–a-chip to evaluate the potential toxicity of nanoparticles, since existing in-vitro cell and tissue culture technologies are not adequate for this task, and using rodents is slow and expensive. Since nanoparticles are becoming increasingly common in daily life there is an urgent need to develop ways to rapidly assess their safety before humans and animals are exposed to them. So they examined how their lab-on–a-chip responded to a variety of nanoparticles, and then compared the results to those of parallel studies performed on the lungs of mice.

A key question was whether inhaled nanoparticles can cross into the bloodstream, several animal studies indicate that they can while in vitro studies suggest otherwise, though as mentioned the relevance of these in vitro methods has been questioned. With the new technology the results were in close agreement, the nanoparticles can cross into the bloodstream. This demonstration indicates that the lab-on-a-chip may provide a suitable platform for future evaluation of aspects of nanoparticle toxicity, as part of new pathways for the evaluation of chemical safety that use as few animals as possible.

So, all in all it is a very great week for building lungs in Science, one to which animal research made a huge contribution.

Paul Browne

1) Patersen T.H. et al. “Tissue-Engineered Lungs for in Vivo Implantation” Science Published Online June 24, 2010 DOI: 10.1126/science.1189345

2) Huh D. et al. “Reconstituting Organ-Level Lung Functions on a Chip” Science Volume 328 (5986), pages 1662 – 1668 (2010) DOI: 10.1126/science.1188302

Addendum

In my rush to finish the above post I forgot to mention another advance in the use of decellularized scaffold and in vitro cell repopulation approach to tissue engineering, scientists at Harvard Medical School produced artificial livers that appeared to function almost as well as normal tissue when transplanted into rats and connected to their blood supply . In the research paper published online in Nature Medicine the authors stress that the artificial liver needs further development before human transplants can be contemplated, but this is further evidence of just how quickly progress is being made in the field of complex tissue engineering.

see more t ..........
http://speakingofresearch.com/2010/06/25/how-to-build-a-lung/

Posted on June 25, 2010 by Blue Sky Science

When you need new lungs

When you need new lungs!


September 21, 2010
People with terminal lung disease may find solace in the recent breakthroughs made in the stem cell research.


Scientists at the Harvard Medical School and Yale University have grown artificial lungs that work in rats using stem cells.

Presently, a lung transplant is the only option for people with terminal lung disease caused by smoking or conditions like cystic fibrosis. However, donor organs are in short supply and rejection is likely even if a lung is available.

To solve both these issues, the researchers stripped original tissue of the donor lungs. The teams then repopulated the remaining connective tissue with foetal stem cells and helped the organs grow.


http://wonderwoman.intoday.in/wonderwoman/story/86607/Health/when-you-need-new-lungs!.html

ECMO Treatment Saves a Critial HIN1 ARDS Patient

ECMO Treatment Saves a Critial HIN1 ARDS Patient
Bangalore | Sep 20, 2010

A 57-year-old former government employee suffering from Acute Respiratory Distress Syndrome (ARDS), following HIN1 infection was successfully treated using Extra Corporeal Membrane Oxygenator (ECMO) system, infusing hope in critical H1N1 ARDS patients in the country.

"This is the first time the ECMO, which is an artificial heart and lung system, was used to treat a lung failure case following HIN1", Dr Binoy, consultant cardiac surgeon with Narayana Hrudayalaya, told media here today.

The cause of death most often in H1N1 cases was due to ARDS or lung failure. He said. In many cases apart from antiviroal antibiotic oselatamivir (Tamiflu), patients were put on ventilator support, which also sometimes failed to save the patient and the only hope in this acute deteriorating stage could now be the ECMO system.

ECMO is a complex system that serves as a heart and lung outside the body. The impure blood is taken out of the body and goes through the machine which purifies it. The oxygenated blood is returned to the body through a system of channels. "Connecting a patient suffering from ARDS to the EMCO, provides the diseased lung with rest required to clear the infection and help it regain its original function", he said.

Though ECMO has been used in cases of cardiac problems in the past, it is for the first time in the country, it was used for lung failure cases arising out of H1N1.

The patient Srinivas, earlier employed with KSRTC, had a bout of cough and cold for a week before he was admitted to a hospital where he was detected with H1N1. He was then put on Tamiflu and was in ICU for four days and had to be subsequently shifted on the ventilator for eight days.

"His condition deteriorated, and the hospital asked us to take my father home as there was no hope", his son said.

However, following a tip off that Narayana Hrudayalaya was trying out the ECMO method, the Narayana Hrudayalaya authorities were asked to chip in. Following which the EMCO was fitted on and he was shifted to Narayana Hrudayalaya.

"Managing the ECMO is the most challenging task as it has to be monitored 24x7. It required an organised effort of team experts including cardiac surgeon, pulmonologist, anaesthetist, critical care specialist, pefusion scientist, physiotherapist and nursing staff", Binoy said.

"The patient was maintained on ECMO for 15 days. His condition gradually improved and we could disconnect the machine. Now the patient has recovered well enough and is expected to be discharged today", said Binoy.

Post ECMO, the status of the patient was normal and he would have to take precautionary steps like any other normal pneumonia patient would have to. There were no long term implications of using the system, he said.

The hospital currently had around six ECMOs which were being used in cardiac patients. Around 100 cardiac patients in last eight years had been put on to ECMO.

This is the second ARDS H1N1 patient put on ECMO. The first patient was put on the machine for 40 days and weaned off. However, after weaning off, his lungs could not regain their normal functioning as they were very badly damaged.

Asked why it had taken nearly a year for the doctors to come up with this treatment, he said though the ECMO system was available, it required considerable expertise to manage it in case of HIN1. The ECMO treatment had been tried out in US and Australia as well where nearly 70 per cent of the patients with ARDS had survived.

He also said that earlier while the death rate was four percent in HIN1, now with virus having been mutated, the death rate was eight percent.

On cost of the treatment, he said that it was still being worked out. However, cost would not be hindering factor at the Narayana Hrudayalaya for those who could not afford it.

Meanwhile, the patient said that he was feeling well.


http://news.outlookindia.com/item.aspx?694124

nice video on alveoli function / how gases are exchanged in your lungs

nice video on alveoli function, how gases are exchanged in your lungs

your respiratory system short video

respiratory system short video

Novalung - Ecmo - to Go / Ecmo

Novalung - Ecmo - "to Go" / Ecmo "light" oxygenates great -less filling


Novalung first for FAI

Thomas Buchsein of fixed-wing a air ambulance provider Flight Ambulance International (FAI) reports on the company´s first use of Novalung technology.

The letters ARC´S (acute respirattory distress syndrome) and All (acute lung injury y) stare for the most severe types of respiratory failure e, which are a common clinical appearance and thhe often lethal common path of a variety of diag gnoses such as pneumonia (including all types of influenza associated chest infections), severe multiple e trauma arc septic shock. Striving always to be att the frontier of mobile intensive care medicine, FFAI used the Novalung iLA (interventional lung as ssist) Membrane Ventilator for the first time, a new w extracorporal ´artificial lung´ technology, to assis st conventional mechanical ventilation in ARDS ppatients arc to prevent the often irreversible lung ttissue damage that is typically associated with aggress sive mechanical ventilation strategies. The system m is characterized by a low-resistance membrane, whicch is integrated in an artificial arterio -venous byp pass. Driven by the patient´s own blood pressure (thu us independent of any mechanical pump and pow wer source), the blood flow is shunted from thee cannulised femoral artery to the also-can nulise eo femoral vein through a small (´•. 4x; 4 cm) plas stic box, containing the core of the system: the af orementioned sophisticated gas-exchanging, he eparin-coated hollow-fibro diffusion membrane, w which does what the patients lungs fail to do -removin ng carbon dioxide and adding oxygen to the blood.

Our first mission with the new sysstem took us to Kuwait, where we had been aske ed not only to transport a patient. but also to as ssist the local medical team with a ven/ challen ging intensive care and mechanical ventilation. T The patient was a 52-year old technical engineer with AARDS subsequent 10 severe bilateral p neumonia and sepsis. From our preflight assessm ment, we were already aware that chest X-rays sshowed a ´white lung´ and that the ventilator was a already set to a very high oxygen concentration o of 90 per cent and a PEEP (peak end-expiratory presssure) of ! 5 mmHg, parameters that wouid normallly dearly forbid any air transport.

The FAI medical team (Dr Gotz L Leonhard, deputy chief medical officer, and Simon n Obier chief paramedic) was for this particularr mission supplemented by Bemd Resio, a very h helpful Novalung Medical Technician and ´rained in ntensive care unit nurse. After the usual general p patient assessment. Dr Leonhard performed a Dopple er-ultrasound examination, relocate and measure sanguine vessels before successfully cannulising thhem. He then connected the iLA-membrane box aand opened the arterio-venous shunt through the iLA-box in which gases and blood are separated only by the aforem mentioned low-resistance diffusion membrane, anaalogous to the natural lung. During the following g hours, it -was possible to gradually adjust the re spirator towards lung protective parameters without the e limitations usually imposed by the need for pulm monary gas exchange. Twenty -four hours lat ter, the patient was considered stable enough to ttake him onboard. The flight was conducted at the s standard cabin pressure of 7,5)00 ft without any a adverse effects - pulsoxymetry, capnometry and b blood gases remained stable throughout the flight.

Summary

The Novalung Membrane Ventilator is a lightweight, low-cost, easy-to-use pumpleess (driven by the patients cardiac output) pulmona ary assist device, clinically already well establishe ed in patients with acute lung failure. \~ is now enterring the world of aero medical transport as a new w and promising asset in helping our patients to survive.

more info on the Novalung

Sherbrooke man survives rare lung surgery

Sherbrooke man survives rare lung surgery


Thu Jul 8, 4:55 PM

Doctors in Sherbrooke, Que. are hopeful that a man suffering from severe pneumonia may have a fighting chance after surviving a rare lung procedure.

The man is believed to be the first in Quebec to have survived the surgery to attach an external artificial lung, known as a Novalung, to his leg.

The device is meant to perform some of the functions of a normal lung, including clearing the body of carbon dioxide and pumping a small amount of oxygen into the body through the arteries and veins in the leg.

The patients involved in the first two surgeries in Quebec did not survive the procedure.


Doctors said the device can only operate for up to 29 days.

It´s going to be there for a short period of time, after a while we´re going to take it out. The device is just to let the lung recover from the pneumonia, said Dr. Marco Sirois, a thoracic surgeon with Sherbrooke University Health Centre.

The 47-year old patient, who cannot be identified due to privacy regulations, is still in critical condition. His daughters said they remain optimistic, despite the fact that their father is still seriously ill.


"Were trying to stay realistic," said Noémie, one of the patient´s daughters.
"But the surgery has given us hope, said the other daughter, Jessica.

The surgery is so rare in Quebec that doctors in Sherbrooke sought the help of a specialist from Toronto, who was flown in from Montreal in a Quebec provincial police helicopter.

The Novalung is also sometimes used to help patients who are waiting for a lung transplant.

see more info on the novalung

Novalung company info and contacts

Novalung company info and contacts

Solutions for Lung Failure


Already today reality: Awake patient with iLA Membrane Ventilator®


Contact info

Novalung GmbH
Egerten 3
D-74388 Talheim


Phone +49 7133 90 11 0
Fax +49 7133 90 11 299

email: info@novalung.com


click to offical website for Novalung.com


Imagine a world in which many patients in the Intensive Care Unit are not placed in an artifical coma so that they can tolerate mechanical ventilation, but rather experience their treatment while awake and breathing easily and spontaneously. Patients who can communicate, eat and drink. This can become reality when a Novalung extracorporeal Membrane Ventilator is used to support the breathing process.

Novalung‘s vision and mission are the creation of new Solutions for Lung Failure using artificial lungs that breathe for the patient outside the body. They thus give the lung Time to Heal® and improve the patient’s quality of life. The iLA Membrane Ventilator® is the first in a series of products that open the door for physicians and nurses to this vision.

Novalung works continuously with its clinical partners to make this vision a reality. We invite you to join us and look forward to an active dialogue!

$5,000 device by Novalung device

Owen Stark in July when he used an artificial lung. He was the youngest patient on the machine. (St. Louis Children's Hospital)

When Owen Stark came to St. Louis Children's Hospital in June with severe lung disease, he had just a few days to live and even fewer options for treatment.
Owen, 2, had severe pulmonary hypertension, meaning the blood vessels in his lungs were so constricted they could barely carry blood. He had to go on life support to keep his heart and lungs functioning. Medications for the disease can take weeks or months to improve a patient's condition. Waiting for a suitable lung transplant can add another two to six months.

"Transplant or medication, both options take time, and he didn't have time," said Dr. Mark Grady, Owen's cardiologist.

A surgeon on the team had heard of an artificial lung used in Europe and Canada, but not approved for long-term use in the United States. The hospital appealed for a compassionate use exemption, which was granted in about three days by the Food and Drug Administration.

Owen's parents, of Eldon, Mo., were shocked by the rapid deterioration of the boy who seemed energetic and healthy just hours before he was hospitalized. They agreed to the experimental treatment.

"We were really nervous about it, but at that point he had no other options to live." Justin Stark said.

Surgeons implanted Owen with the Novalung device, a small box with two tubes on either side that are attached to the heart. Blood goes through one tube into the box, where oxygen is added and carbon dioxide is removed, and then the blood returns to the heart through the other tube.

Hospital officials were eager to promote the story to the public, as the first time the $5,000 device had been used on a patient in the U.S.

But Owen's doctors resisted public and media attention until they knew Owen wasn't going to die.

After about three weeks on the device, Owen was feeling pretty vigorous, and kicked one of the tubes loose. Somehow a blood clot dislodged and the little boy suffered a stroke.

The doctors decided to remove the device, and Owen has been breathing on his own ever since.

Owen lost mobility on his right side and his speech was affected by the stroke. He's in therapy and still takes three drugs for lung function.

Doctors say they're in a wait-and-see mode. Owen's lungs could stop functioning again and he might still need a lung transplant. Or he could leave the hospital and go home in a month.

"His prognosis is guarded," Grady said. "He's clearly shown a good response to the meds. Only time will tell whether he'll stabilize."

NovaLung on an emergency basis

Currently, the Novalung ILA is listed as a “Class III – Premarket Approval” device by the Food and Drug Administration, the category with the most stringent approval requirements, according to the FDA’s Web database.

“When an Army doctor wants to use the NovaLung on an emergency basis, we ask the manufacturer, NovaLung U.S., to notify the FDA of the device’s use under the FDA NovaLung Investigational Device Exemption requirements,” wrote Cynthia Vaughn, a spokeswoman for the Army surgeon general’s office, in an e-mail to Stars and Stripes.


But despite any after-the-fact scrutiny or investigations made into medical staff over use of the device last spring, doctors said they were simply doing what they could do to save wounded servicemembers. “We tried to do what we would want someone to do if it was our own son, daughter, or spouse; each and every life was precious,” Col. Rhonda Cornum, commander of Landstuhl at the time Mishoe, Phillip and Wong were hurt, wrote in an e-mail to Stars and Stripes.

Doctors did — and continue to do — everything they can to save injured servicemembers, said Col. Mark Ivey, a pulmonary critical care specialist who assisted Boylston with both Phillip and Wong. “We can and will do whatever it takes to return [servicemembers] home in as good of shape as possible,” Ivey said.

And though her son has no recollection of being attached to the Novalung ILA, Julie Mishoe said she knows it helped save his life, and was glad that its success with Joshua may have helped make it available to other servicemembers. “It’s just wonderful to know that machine has been used to save other people’s lives,” she said.


click to read more at stripes.com news lung device German NovaLung

drawing of the Novalung, made in Germany

The Novalung ILA aids the lungs by drawing off carbon dioxide from the blood and infusing cells with oxygen. Inserted by catheters into the major arteries in the thighs, it relies on the patient’s heartbeat to pump blood out of one leg, across the special membrane that performs the transfer and back into the body through the other leg.

First Working Replacement Lung Created in Lab

First Working Replacement Lung Created in Lab

An engineered lung (bottom) worked when implanted into a rat (top).

For the first time scientists have reconstructed working lungs in the lab and transplanted them into a living animal. The achievement is a breakthrough in biomedical engineering that could lead to replacement lungs for humans in the near future, experts say.
that's vulnerable to tissue rejection.



In a new study, researchers took lungs from a living rat and used detergents to remove lung cells and blood vessels, revealing the organ's underlying matrix. This lung "skeleton"—made of flexible proteins, sugars, and other chemicals—consists of a branching network that divides more than 20 times into smaller and smaller structures. (See an interactive graphic of lung structure.)



The researchers placed these "decellularized" lungs into a bioreactor, a machine filled with a slurry containing different types of lung cells extracted from rat fetuses. Within several days, the fetal cells naturally attached to the lung matrix and formed a functional lung.

"By and large, the correct subsets of cells went to their correct anatomical locations," explained study leader Laura Niklason, a biomedical engineer at Yale University. "It appears that the lung matrix has cues, or 'zip codes,' that tell the cells where to land."

When the team implanted the engineered lungs into an adult rat for short periods of time—between 45 minutes and two hours—the lungs exchanged oxygen and carbon dioxide in the same way as natural lungs.
"Leap Forward"

By using a natural lung matrix, Niklason's team has avoided one of the biggest hurdles of lung-regeneration attempts—finding a suitable "scaffold" for lung cells to attach to.
Because manufacturing techniques cannot yet replicate nature's complex design, attempts to create synthetic scaffolds have been unsuccessful. Niklason spent several years trying to create a synthetic lung scaffold, but in the end concluded it was too difficult.


"I decided I couldn't do it, and probably nobody else could either," she said.

The new research represents a "real leap forward" in lung regeneration, said Peter Lelkes, a biomedical engineer at Drexel University in Philadelphia.

"People have engineered organs such as bone and cartilage before, but by comparison to the lung, these are all kids' games," added Lelkes, who was not involved with the study.

Stem Cell Hurdle
Niklason estimates it will be about 20 to 25 years before her team's technique can be used in humans.
That's because a few technical and scientific challenges remain.

Chief among these is finding ways of creating stem cells—which can transform into any other type of cell—from patients with lung disease. No techniques currently exist for creating such cells, which would carry no risk of immune rejection.

(Related: "Liposuction Fat Turned Into Stem Cells, Study Says.")
"The stem cell issue," Niklason said, "is really the big fundamental scientific hurdle."

The research is detailed in this week's issue of the journal Science
Ker Than for National Geographic News

published June 24, 2010

see more at news nationalgeographic com news replacement lab

NovaLung in use with a 2 year old in Missouri

NovaLung in use with a 2 year old in Missouri

Toddler Is World’s Youngest Recipient of Artificial Lung


With the help of German-made NovaLung, 2-year-old Missourian Owen Stark is breathing easily.

When toddler Owen Stark's heart stopped beating not once, but 10 times, his parents thought they would lose him forever. Having been unsuccessful in waiting for a lung donor, they agreed to try an artificial lung device — with successful results.

It was during a shopping trip that the previously healthy 2-year-old collapsed near his Missouri home and was rushed to hospital, unable to breathe, reports Britain's Daily Mail. Diagnosed with idiopathic pulmonary hypertension (high blood pressure in the lungs), he was put on a heart/lung bypass machine at St Louis Children's Hospital while the search for a suitable donor began.

Patients can only be kept on a bypass machine for a limited time before it causes irreversible damage, so time was running out. His parents made the brave decision to try something new: a German-built artificial lung device, called NovaLung. It was the first time a patient as young as their son had been fitted with the device.

Placed outside the body, the little white box is attached by two tubes removing carbon dioxide outside the human lung and perfused with blood by the heart like a natural organ. Doctors have been amazed by Stark's response to his sessions on the machine. Pediatric cardiologist at the hospital, Dr. Mark Grady said, "This absolutely saved his life. He could be going home within a month, which we never ever thought would be possible."

Expected to lead a relatively long and happy life thanks to his new treatment, Stark's parents couldn't be happier. Owen's mother Tonya Stark added, "His life expectancy has gone from a few days to a few weeks and now years — it's a miracle."

By Monique Jessen
 September 1, 2010


toddler gets the Novalung artificial lung, click for more info

Artificial lungs breathe new hope for transplants

Artificial lungs breathe new hope for transplants


First it was the heart, then the liver - now two research teams have grown artificial lungs that function in rats. It is hoped that a similar technique could one day engineer donor organs for humans.

A lung transplant is the only option for people with terminal lung disease caused by conditions like cystic fibrosis or chronic obstructive pulmonary disease. But donor organs are in short supply, and rejection is likely even if a lung becomes available.

In a quest to solve both problems, teams from Harvard Medical School in Boston and Yale University, working separately, stripped donor rat lungs of their original tissue by exposing them to a mild detergent. The teams then repopulated the remaining "scaffold" of connective tissue with foetal stem cells and incubated the organs in nutrients to help them grow.

The new lungs were then "replumbed" into rat recipients. The regenerated lungs resembled native lungs in size and oxygenated the recipient's blood for up to six hours, after which oedema - accumulation of fluid within the lung - and capillary leakage occurred.



cick to see the site newscientist.com artificial lungs breathe new hope