more work on lung stem cells and emphysema

Cell transplantation of lung stem cells has beneficial impact for emphysema

Tampa, Fla. (June 4, 2012) – When autologous (self-donated) lung-derived mensenchymal stem cells (LMSCs) were transplanted endoscopically into 13 adult female sheep modeled with emphysema, post-transplant evaluation showed evidence of tissue regeneration with increased blood perfusion and extra cellular matrix content. Researchers concluded that their approach could represent a practical alternative to conventional stem cell-based therapy for treating emphysema.
The study is published in Cell Transplantation (21:1), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.


"Mensenchymal stem cells are considered for transplantation because they are readily available, highly proliferative and display multi-lineage potential," said study corresponding author Dr. Edward P. Ingenito of the Brigham and Women's Hospital Division of Pulmonary and Critical Care Medicine. "Although MSCs have been isolated from various adult tissues - including fat, liver and lung tissues - cells derived from bone marrow (BM) have therapeutic utility and may be useful in treating advanced lung diseases, such as emphysema."


However, according to the authors, previous transplantation studies, many of which used an intravenous delivery method, have shown that BM-MSCs have been only marginally successful in treating lung diseases. Further, therapeutic responses in those studies have been limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury.

To try and answer the questions surrounding the utility of BM-MSCs for treating advanced emphysema, a disease characterized by tissue destruction and loss of lung structural integrity, for this study the researchers isolated highly proliferative, mensenchymal cells from adult lung parenchyma (functional tissue) (LMSCs) and used an endoscopic delivery system coupled with a scaffold comprised of natural extracellular matrix components.
"LMSCs display efficient retention in the lung when delivered endobronchially and have regenerative capacity through expression of basement membrane proteins and growth factors," explained Dr. Ingenito.

However, despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. Cell death likely occurred because of the failure of LMSCs to home to and bind within their niche, perhaps because the niche was modified by inflammation or fibrosis. These cells are attachment-dependent and failure to attach results in cell death."
Their findings did suggest, however, that LMSCs were capable of contributing to lung remodeling leading to documented functional improvement rather than scarring 28 days post transplantation.
"Although the data is from a small number of animals, results show that autologous LMSC therapy using endoscopic delivery and a biocompatible scaffold to promote engraftment is associated with tissue remodeling and increased perfusion, without scarring or inflammation," concluded Dr. Ingenito. "However, questions concerning mechanism of action and pattern of physiological response remain topics for future investigation."

"The impact of mesenchymal stem cells derived from autologous lung tissue demonstrated in this study, suggests that transplantation of these cells could prove to be an important factor in the treatment of emphysema, though further studies are required" said Dr. Amit N. Patel, director of cardiovascular regenerative medicine at the University of Utah and section editor for Cell Transplantation.

###

Contact: Edward P. Ingenito, MD, PhD, Pulmonary and Critical care Medicine, Brigham and Women's Hospital, 75 Francis St. Boston, MA, USA.
Tel.(617) 833-8531
Fax. (617) 732-7421
Email eingenito@partners.org
Citation: Ingenito, E. P.; Tsai, L.; Murthy, S.; Tyagi, S.; Mazan, M.; Hoffman, A. Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant. 21(1):175-189; 2012
The Coeditor-in-chief's for Cell Transplantation are at the Diabetes Research Institute, University of Miami Miller School of Medicine and Center for Neuropsychiatry, China Medical University Hospital, TaiChung, Taiwan. Contact, Camillo Ricordi, MD at ricordi@miami.edu or Shinn-Zong Lin, MD, PhD at shinnzong@yahoo.com.tw or David Eve, PhD at celltransplantation@gmail.com
News release by Florida Science Communications


see the orginal source on this article

Scientists find possible lung stem cell

Scientists find possible lung stem cell

Scientists find possible lung stem cell, could lead to new therapies for emphysema, other ills

 

NEW YORK, N.Y. - Scientists believe they've discovered stem cells in the lung that can make a wide variety of the organ's tissues, a finding that might open new doors for treating emphysema and other diseases.

When these human cells were injected into mice, they showed their versatility by rebuilding airways, air sacs and blood vessels within two weeks. One expert called that "amazing."
While stem cells have been found in bone marrow and some other parts of the body, it hasn't been clear whether such a versatile cell existed in the lung.
Experts not involved in the study stressed that the work must be confirmed by further research and that it's too soon to make any promises about therapies. But they said it could be a significant advance in a difficult field of research.
"These are remarkable findings and they have extraordinary implications," said Dr. Alan Fine of Boston University, who called the mouse results amazing. "But it has to be replicated."

Stem cells can produce a wide variety of specialized kinds of cells. Scientists are working to harness them as repair kits for fixing damage from diseases like Parkinson's and diabetes. Most people have heard about embryonic stem cells, which have caused controversy because embryos must be destroyed to recover them.

In contrast, the new lung cell would be an "adult" stem cell, like others found in the body. Adult stem cells maintain and repair the tissues where they're found. The bone marrow cells, for example, give rise to various kinds of blood cells, and they've been used for years in transplants to treat leukemia and other blood diseases.

The lung work is reported in Thursday's issue of the New England Journal of Medicine by Drs. Piero Anversa and Joseph Loscalzo and colleagues at Brigham and Women's Hospital in Boston. In a telephone interview, Anversa said it's not clear what the lung stem cell normally does but that he thinks it's involved in replacing other lung cells lost throughout life.

Loscalzo said it's too early to tell what lung diseases might be treated someday by using the cells. He said researchers are initially looking at emphysema and high blood pressure in the arteries of the lungs, called pulmonary hypertension. Emphysema is a progressive disease that destroys key parts of the lung, leaving large cavities that interfere with the lung's function.

Anversa said the cells may also prove useful to build up lungs after lung cancer surgery. It's not clear whether they could be used in treating asthma, he said.
While a lung stem cell theoretically could be used to grow a lung in a lab for transplant, Loscalzo said that would be very difficult because the lung is so complex. Instead, he said, scientists will first look at isolating the cells from a patient, multiplying them in the laboratory, and then injecting them back into the patient's lung.
The mouse experiments showed "the cells are smarter than we are," able to build normal lung structures in an injured lung, he said.

The researchers found the cells in donated surgical samples of adult tissue. The same cells appeared in tissue donated from nine fetuses that had died, giving evidence that the cells are present before birth and perhaps participate in lung development. To study the cells' behaviour, researchers injured lungs of mice and then injected six doses of about 20,000 cells apiece.

Within 10 to 14 days, the injected cells had formed airways, blood vessels and air sacs. "We had a very large amount of regeneration" involving millions of new cells, Anversa said.
The new tissue showed "seamless" connection to the rest of the lung, and researchers believe it would work, although that wasn't tested, Loscalzo said. The results appeared in all 29 mice tested.

Dr. Brigitte Gomperts at the Broad Stem Cell Research Center at the University of California, Los Angeles, said scientists have been hotly debating whether a single stem cell type could give rise to the more than 40 cell types in the lung __ cells that do such different jobs as protecting the body from inhaled germs and exchanging oxygen for carbon dioxide. It's a technically difficult question to study, said Gomperts, who was not involved in the new work.

If the new results can be confirmed, "it's a significant advance" that will help in understanding normal lung repair and abnormal repair found in disease, she said.
The work was supported by the National Institutes of Health and a Swiss foundation.

click to read more info on lung stem cells for emphysema

Stem cells used for Lungs

Stem cells that are able to regenerate damaged lung tissue have been discovered by scientists. The brochioalveolar stem cells (BASCs), naturally present in the lungs of rodents and humans, are capable of rebuilding alveoli - the small air sacs in lungs.
Professor Frank McKeon, from the Genome Institute in Singapore and Harvard Medical School, hopes that the discovery of the stem cells will lead to new treatments for people with damaged lungs. 'We have found that the lungs do in fact have a robust potential for regeneration, and we've identified the specific stem cells responsible', he said.


The stem cells were isolated after researchers infected mice with a form of the H1N1 influenza virus - similar to the virus that caused the 1918 flu pandemic - to observe lung damage and regeneration. The virus initially damaged more than half of the lung alveolar tissue, but the alveoli had regenerated by three months after infection. There was no sign of lung fibrosis, a chronic scarring condition commonly seen after other forms of lung damage.

'We saw essentially pristine lungs at three months after a loss of 50 percent of lung tissue', said Professor McKeon, who led the team.
The cells multiply rapidly, migrate towards areas of damage in the lungs and assemble into 'pods' that go on to form new alveoli. Similar stem cells with the ability to multiply and form pod-like structures were also isolated in human lung tissue.
Researchers are now working to identify the signalling molecules and growth factors that promote lung regeneration at repair sites. Such work could result in improved therapies for acute and chronic lung damage caused by conditions such as asthma, chronic obstructive pulmonary disease and pulmonary fibrosis.

'These findings suggest new cell- and factor-based strategies for enhancing lung regeneration following acute damage from infection, and even in chronic conditions such as pulmonary fibrosis', said Professor McKeon. 'It's too early to say common lung diseases will be treatable, but it's a start, and there's a lot of potential'.
In another study, also published in the journal Cell, researchers at the Howard Hughes Medical Institute and Weill Cornell Medical College identified a key signalling molecule involved in regenerating alveoli and lung tissue.

The molecule - matrix metalloproteinase 14 (MMP14) - is required for the growth of new alveoli. When one lung is removed, new alveoli are known to grow in the other intact lung. But when the researchers blocked the activity of MMP14, the lung's regenerative capacity was impaired. Reintroducing MMP14 restored regeneration. The researchers found that cells in the blood vessels of the lungs produced MMP14.
'The key is that the blood vessels turn on the pathways for regeneration', said Dr Shahin Rafii, who led the research; 'the therapeutic potential is tremendous'.

SOURCES & REFERENCES

Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection

Cell | 28 October 2011

Lung stem cells offer therapeutic clues

EurekAlert! | 27 October 2011

Regenerated Lungs from Stem Cells Bring Possible Therapy

International Business Times | 27 October 2011

Stem Cells that Rebuild Alveoli After Acute Respiratory Distress Syndrome Identified

Genetic Engineering & Biotechnology News | 28 October 2011

Stem-cell find breathes new life into lung repair

New Scientist | 28 October 2011 see complete article om stem cells and growing new lungs

Stem cells used to regenerate lungs?

Stem cells used to regenerate lungs?

Working together, scientists and clinicians make research breakthrough that paves the way for novel therapies for respiratory diseases

Scientists at A*STAR'S Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration.

Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide.

The team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs - nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs) and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro.

"We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway", said Dr Wa Xian, Principal Investigator at IMB. "This is a big advancement in the understanding of adult stem cells that will encourage further research into their potential for regenerative medicine."
Using a mouse model of influenza, the team showed that after infection, DASCs rapidly grow and migrate to influenza-damaged lung areas where they form "pods". These "pods" mature to new alveoli which replace the alveoli that were destroyed by the infection, leading to lung regeneration.

"We have harvested these "pods" to provide insight into genes and secreted factors that likely represent key components in tissue regeneration.
These secreted factors might be used as biological drugs (biologics) to enhance regeneration of the lung and airways," said Dr Frank McKeon, Senior Group Leader of the Stem Cell and Developmental Biology at GIS.
The research was jointly led by Dr Frank McKeon from GIS and Dr Wa Xian from IMB in collaboration with scientists at the National University of Singapore (NUS), and clinicians at the Harvard Medical School and the Brigham and Women's Hospital in Boston.

Prof Birgitte Lane, Executive Director of IMB, said, "This groundbreaking work is a fine example of collaborative research, which has brought us new insight into lung epithelial stem cells. This will have breakthrough consequences in many areas." Dr Edison Liu, Executive Director of GIS, added, "We will continue to seek impactful collaborations and build upon this research area where there is a need for novel therapies, which will offer hope for patients suffering from respiratory diseases."




click to read more on this adance in lung therapy in lung regeneration