Navigation Links
Researchers Develop First Mouse Model of Lung Transplantation

Surgeons at Washington University School of Medicine in St. Louis have developed the first mouse model of lung transplantation , and theyre hoping it will help explain why the success of the procedure in humans lags far behind other solid organ transplants.

Ultimately, the mouse model could pave the way for developing new therapies to prevent lung transplant rejection a major problem that limits the long-term success of the procedure.

Five years after lung transplant surgery, only about 45 percent of patients are still alive, according to the U.S. Organ and Procurement and Transplantation Network. This compares with five-year survival rates of about 70 percent for heart and liver transplants and about 80 percent for kidney transplants. About 1,000 lung transplants are performed each year in the United States.

The high failure rate of lung transplants is a huge problem, says lung transplant surgeon Daniel Kreisel, M.D., Ph.D., an assistant professor of surgery and a lead investigator of the research.

Unlike other organs, lungs are constantly exposed to bacteria and viruses in the environment, and we think this exposure increases the risk of chronic rejection and the eventual failure of the organ. This is why the mouse model is so critical. It will allow us to understand the molecular mechanisms that control lung transplant rejection, he added.

Lung transplants are the only treatment option for end-stage lung disease, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary fibrosis and certain congenital lung defects. Following a transplant, patients must take drugs for the rest of their lives that suppress the immune system and prevent it from attacking the new lung. This leaves them vulnerable to upper respiratory infections, which can quickly develop into pneumonia.

Kreisel and others suspect that these illnesses alter the immune response and increase inflammation, which eventually lead to chronic rejection. They note that mainstay immunosuppressive drugs simply are not effective at preventing chronic rejection for lung transplants, and they hope the mouse model will reveal why.

The current hypothesis is that lung transplant rejection is linked to chronic inflammation from transient viral or bacterial infections, and this can be aggravated by the fact that transplant recipients are taking immunosuppressive drugs, Kreisel said.

Mouse models for heart, liver and kidney transplants have existed for years, but developing a similar model for lung transplantation has proved to be a real technical challenge. Mouse lungs measure less than an inch in length and the pulmonary vein and artery, which carry blood to and from the heart, are as thin as human hair.

Mikio Okazaki, M.D., a postdoctoral fellow, adapted the lung transplantation technique used in rats to the mice. He uses synthetic cuffs to join the donor vessels with those of the recipient. Okazaki has successfully performed several hundred lung transplants in the mice, and the teams analysis indicates the model simulates the same immune response that occurs in humans following lung transplantation.

Before Okazaki and his Washington University colleagues developed the mouse model, researchers had been studying lung transplantation using a nonphysiological mouse model in which a small section of trachea from one mouse was transplanted under the skin of another. Although it was simple to create, the model did not accurately mimic lung transplantation.

It was a very artificial model that had little to do with reality. We think the new model will be far better for studying the underlying immune mechanisms that lead to rejection, Okazaki said.

The new mouse lung transplant model has an advantage over those in rats and larger animals because the genetics of mice are well documented a nd their genes are easier to manipulate.

With the mice, we can selectively delete genes to study their function in the transplanted lung or in the recipient, which weve not been able to do effectively in other animal models, said Andrew Gelman, Ph.D., an assistant professor of surgery, who is a lead investigator of this research.

By understanding the genes that control lung graft survival, researchers will be able to better guide the development of therapies to counteract chronic rejection, he added.

The mouse model also will allow the researchers to investigate how other transplant-related complications affect the long-term success of the procedure. Many lung transplant patients experience gastric reflux, and doctors suspect this acid exposure damages the lining of the lung and further exposes the organ to pathogens. The mouse model will let researchers evaluate whether gastric reflux increases the risk of lung rejection.

Additionally, the time between surgery to harvest a donor lung and transplant it into a patient is widely suspected to affect its overall function after transplant surgery. The mouse model will help pinpoint the inflammation that underlies damage to the organ when it cant be transplanted quickly and may lead to ways to prevent such injury.

Based on mouse models of other solid organ transplants, researchers have learned that different groups of immune cells contribute to rejection in different organs.

Rejection of the lung differs from rejection of the heart in terms of the cells that participate in that rejection, said Alexander Sasha Krupnick, M.D., assistant professor of surgery.

Every organ is different. What weve learned about rejection of the heart in mice does not apply to lungs. So we are thrilled to finally have an acceptable mouse model of lung transplantation to help us discover ways to increase the success of these transplants in humans, he added.

The mouse model is described in the June issue of the American Journal of Transplantation.


'"/>




Related medicine news :

1. Researchers urge caution in using ear tube surgery
2. Researchers Scale to assess the Severity of Epilepsy in Kids
3. Researchers trick Alzheimers Enzyme
4. Researchers find new HIV hiding place
5. New Hair in 15 Days Could Now Be A Possibility Say Researchers
6. Researchers developed world’s smallest toothbrus
7. Researchers discover receptor cells that can cause epilepsy
8. 15 Anti-SARS Drugs Identified By China-Europe Team of Researchers
9. Researchers reversed the process of memory loss
10. Researchers Identify Key Gene That May Help Brain Treatment
11. Researchers Discover Protein That Causes Malaria
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:9/20/2017)... ... 2017 , ... Recognising that in today’s busy world consumers ... positive results in just three weeks. Setting the groundwork for a healthier lifestyle, ... into hectic work and family schedules, participants can lose up to 15lbs during ...
(Date:9/20/2017)... ... September 20, 2017 , ... Ron Norman, CEO ... marketers this week about the value of senior executives, pointed to a quote ... in business has brought us to the present and will lead us into ...
(Date:9/20/2017)... ... ... “Monique”: is the story of Monique, whose mother’s deteriorating physical condition forces the ... has owned four beauty salons and written a book regarding the author’s success in ... , “The doctor’s office was only three blocks away, and she could walk it, ...
(Date:9/19/2017)... ... September 19, 2017 , ... Trusted debt-reduction firm CreditAssociates, LLC has ... translating to in excess of $835 million in resolved debt for its clients. , ... are some of the categories of debt settled by the company. With more than ...
(Date:9/19/2017)... ... September 19, 2017 , ... The ... Canyon Ranch to its recently formed Corporate Roundtable, a group of individuals ... and a sustainable world. , Canyon Ranch is a unique collection of lifestyle-based ...
Breaking Medicine News(10 mins):
(Date:9/18/2017)... Sept. 18, 2017 EpiVax, Inc. ... bioinformatics and immune engineering, today announced a ... A (H7N9) vaccine. ... seasonal influenza and presents a challenge for ... exposure to be effective. Using state-of-the-art bioinformatics and ...
(Date:9/9/2017)... WASHINGTON , Sept. 8, 2017 ... Mobile MRI Unit coming to Washington DC ... When: Tuesday, September 12 th – Monday, ... to Washington, D.C. offering free MRI brain scans to the public.Where:  ... – will be parked at 501 K Street NW, Washington, D.C.What:BTF brings ...
(Date:9/7/2017)... Texas , Sept. 7, 2017 ... science focused on fulfilling the promise of precision ... further validate the benefits of its molecular profiling ... study utilized comprehensive genomic profiling plus (CGP+) with ... individual patient,s tumor on a molecular level, leading ...
Breaking Medicine Technology: