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