The Methuselah Foundation Blog

November 14, 2011

Cardiac Stem Cell Test Breakthrough in Treating Heart Failure



heart failure.jpg

Heart failure occurs when a damaged heart is weakened
and unable to pump enough blood around the body
(Photo: ALAMY)



For the first time in human history, cardiac stem cells were used to repair the severely damaged hearts of 16 patients in a trial conducted by researchers from the University of Louisville in the US. "It could offer an entirely new option and a potential cure for patients who are now dying from heart failure," said study author Dr. Roberto Bolli, director of cardiology at the University of Louisville in Kentucky. "The results are striking. While we do not yet know why the improvement occurs, we have no doubt now that ejection fraction increased and scarring increased."

The ejection fraction or "pumping efficiency" of the hearts of eight patients had improved by more than a whopping 12%. These results tripled the 4% improvement the researchers were expecting to see.

"If these results hold up in future studies, I believe this could be the biggest revolution in cardiovascular medicine in my lifetime, " said an impressed Professor Bolli.

The "Schipio" trial included a total of 23 patients, all of whom suffered heart failure due to a previous heart attack. Seven of these received standard care while the other sixteen were assigned to stem cell therapy. The groundbreaking treatment involved extracting cardiac stem cells (CSCs) from patients during bypass surgery. CSCs are self-renewing cells that rebuild hearts and arteries. After a purification process and a period of growth in the laboratory, the cardiac stem cells are then injected back into damaged regions of the patient's hearts four months later. A million of these CSCs were injected into each patient via a balloon catheter, an expandable device used to open up arteries.

Interestingly, this small Phase I study was primarily designed to assess safety rather than effectiveness of the new, cutting-edge treatment. At the start of the study, the patients had an average left ventricular ejection fraction (LVEF) of 40% or lower. Normal LVEF is 50% or higher. Over a period of 4 months, patients who received the treatment saw an 8.5% improvement in LVEF, increasing to 12.3% after one year. LVEF did not change in the seven patients of the "control" group who did not undergo the cardiac stem cell therapy. MRI scans conducted on number of patients revealed that cardiac scarring had been reduced.

"Michael Jones, our first patient, could barely walk 30 feet [before treatment]," Dr. John H. Loughran said. "I saw him this morning. He says he plays basketball with his granddaughter, works on his farm, and gets on the treadmill for 30 minutes three times a week. It is stories like that that makes these results really encouraging."

These findings are published in the online edition of The Lancet medical journal and will be presented at the American Heart Association's Scientific Sessions meeting in Orlando, Florida. Now, Professor Bolli and his team intend on applying for funding a much bigger, multi-centre Phase II trial.

Professor Gerd Heusch from the University School of Medicine in Essen, Germany commented on the study in The Lancet: "The results from Scipio raise new optimism because the study is based on rigorous quality standards and the reported benefits are of an unexpected magnitude... we will have to see whether the further data will meet the promises of the present study. More patients will need to be followed up over a longer period."





Reference:

"Stem Cell Test Is 'biggest Breakthrough in Treating Heart Attacks for a Generation'" The Telegraph. Telegraph Media Group Limited, 14 Nov. 2011. Web. 14 Nov. 2011.
http://www.telegraph.co.uk/health/healthnews/8889031/Stem-cell-test-is-biggest-breakthrough-in-treating-heart-attacks-for-a-generation.html.

November 11, 2011

Pituitary Glands Grown from Scratch



pituitary.jpgResearchers led by Dr. Yoshiki Sasai from the RIKEN Centre for Developmental Biology in Kobe, Japan constructed retina-like structures from cultured mouse embryonic stem cells last Spring. Their achievement this week is truly an amazing feat-- constructing a pituitary gland from mouse stem cells.

The pituitary gland is a pea-sized endocrine gland at the base of the brain that secretes hormones like Human Growth Hormone (HGH) and thyroid stimulating hormone (TSH) that play key roles in human growth, pregnancy, blood pressure, and thyroid function. It's especially crucial during early development, so armed with the ability to simulate the formation of the pituitary gland could help researchers better understand how these developmental processes function. Hormone disorders result from inadequate release of certain hormones like these by the pituitary gland. Growth disorders such as gigantism, vision problems, and even blindness are also associated with disruptions in the pituitary.

This study, published in this week's issue of Nature, is a crucial step forward in medical science's ability to bioengineer complex organs for human transplantation.

Using a three dimensional culture, the team placed the mouse stem cells in a manner that mimics the way a pituitary gland naturally grows in the embryo. The gland is naturally made up of two different tissue types in the brain. The culture in the study was set up so that these two tissues would come together as they do in the brain.

After 13 days in culture, mouse embryonic stem cells
had self-assembled the precursor pouch, shown here,
that gives rise to the pituitary gland.
Nature



"Using this method, we could mimic the early mouse development more smoothly, since the embryo develops in 3-D in vivo," says Yoshiki Sasai, the lead author of the study.

Rathke's pouch - a fold of tissue - formed naturally and grew into the pituitary gland after about two weeks. Prior to this, the researchers only had a vague sense of the signaling factors necessary to form a pituitary gland, but after trial and error, the winning combination involved two main steps, requiring the addition of two growth factors and a drug called "sonic hedgehog" to stimulate a developmental protein. Then, the researchers tested the functionality of their synthesized organs by transplanting the tissue into mice with pituitary dysfunction. The transplants were a success! Levels of glucocorticoid hormones in the blood and behavioral symptoms such as lethargy were stabilized. The mice's hormone levels soon returned to normal.

"This is just an initial step toward generating viable, transplantable human organs, but it's both an elegant and illuminating study," says Michael G. Rosenfeld, a neural stem-cell expert at the University of California, San Diego.

Next, Sasai and colleagues will be attempting the experiment with human stem cells. Sasai suspects it will take them another three years to synthesize human pituitary tissue and perfecting the transplantation methods in animals might take another few years. Still, researchers in the stem-cell field and biomedical researchers on the whole are impressed with what Sasai's team has accomplished. Yet another small victory aimed for the big win!




Reference:

Westly, Erica. "Researchers Create a Pituitary Gland from Scratch." Technology Review. MIT Technology Review, 9 Nov. 2011. Web. 11 Nov. 2011. http://www.technologyreview.com/biomedicine/39108/?p1=A1.

November 2, 2011

Lung Regeneration May Soon Be a Reality



lungs.jpegThe October 28, 2011 issue of the journal Cell reports that researchers at Weill Cornell Medical College have uncovered the biochemical signals in mice that trigger generation of new lung alveoli, the countless tiny champagne grape-like sacs within the lung where oxygen exchange takes place. The team claim that they have taken an important step forward in their quest to "turn on" lung regeneration. This research may effectively treat millions suffering from respiratory disorders.

It's common knowledge in the biomedical industry that mice have the ability to regenerate and even expand the capacity of one lung if the other is missing--this study identifies the specific molecular triggers behind this adaptive process. The researchers believe these findings are quite relevant to human beings.

Dr. Shahin Rafii, the Arthur B. Belfer Professor of Genetic Medicine and co-director of the Ansari Stem Cell Institute at Weill Cornell Medical College and this study's lead investigator said "Several adult human organs have the potential upon injury to regenerate to a degree, and while we can readily monitor the pathways involved in the regeneration of liver and bone marrow, it is much more cumbersome to study the regeneration of other adult organs, such as the lung and heart."

"It is speculated, but not proven, that humans have the potential to regenerate their lung aveoli until they can't anymore, due to smoking, cancer, or other extensive chronic damage," says Dr. Rafii, who is also an investigator at the Howard Hughes Medical Institute. "Our hope is to take these findings into the clinic and see if we can induce lung regeneration in patients who need it, such as those with chronic obstructive pulmonary disease (COPD)."

Dr. Rafii and his colleagues previously uncovered growth factors that control regeneration in the liver and bone marrow. In both cases, they found that endothelial cells produce the key inductive growth factors, described as "angiocrine factors". The current lung study revealed the same phenomenon: Blood vessel cells in the lungs jump-start alveoli regeneration. "Blood vessels are not just the inert plumbing that carries blood. They actively instruct organ regeneration," says Dr. Rafii. "This is a critical finding. Each organ uses different growth factors within its local vascular system to promote regeneration."

In the study, the left lungs of mice were removed for Dr. Bi-Sen Ding to examine the biochemical process of the remaining lung's regeneration. According to a prior investigation by Dr. Crystal, once the left lungs were removed, the right lungs regenerated by 80%. It replaced the majority of the lost alveoli. They discovered that when the left lung is removed, receptors on endothelial cells in the lung that respond to basic fibroblast growth factor and vascular endothelial growth factor is triggered.

Research lead Dr. Shafin Rafii explained: "Several adult human organs have the potential upon injury to regenerate to a degree, and while we can readily monitor the pathways involved in the regeneration of liver and bone marrow, it is much more cumbersome to study the regeneration of other adult organs, such as the lung and heart [...]"

Co-author Dr. Ronald G. Crystal said "There is no effective therapy for patients diagnosed with COPD. Based on this study, I envision a day when patients with COPDD and other chronic lung diseases may benefit from treatment with factors derived from lung blood vessels that induce lung regeneration."





Reference:

Rattue, Grace. "Lung Regeneration May Be A Reality Soon." Medical News Today. Medical News Today, 1 Nov. 2011. Web. 2 Nov. 2011. http://www.medicalnewstoday.com/articles/236928.php.


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