Pulmonary hypertension is high blood pressure in the arteries leading to the lungs. There is no cure for the disease, but there are treatments that help to ease some of the symptoms of the disease. The vessels that carry blood from the heart to the lungs become hard and narrow in patients with pulmonary hypertension.

Over time, the heart will weaken and may result in heart failure since the condition makes it more difficult for the heart to pump blood. Available treatments for the disease range all the way to lung transplant, with oxygen therapy and drugs being less aggressive forms of therapy.

The condition is relatively rare. Among people with the disease, there were 260,000 hospital visits and 15,668 deaths in 2002. 807,000 people with pulmonary hypertension were hospitalized during the two years spanning 200 and 2002. Thirty-four percent of those hospitalizations were younger than age 65, and 61 percent were among women.

Today, their is a great deal of chatter about an innovative approach to treating pulmonary hypertension. Cell therapy is being combined with gene therapy in order to treat patients. No blood vessel or heart disease has ever been treated using combined cell and gene therapy. This approach marks a first.

Using adult stem-like cells called endothelial progenitor cells (EPC), researchers from St. Michael’s Hospital in Toronto are treating patients with pulmonary hypertension. Damage occurs to the endothelial cells which line the blood vessels of the lungs in people suffering from the disease.

“The one thing that all endothelial cells have in common is that they are replaced by circulating endothelial progenitor cells. We all have in our blood a very small proportion of cells that circulate freely in our blood that have the capacity to become healthy endothelial cells when they are in the right environment. We think that those cells are there to repair blood vessels that are damaged,” Dr. Michael Kutryk, from St. Michael’s Hospital, said.

The EPCs are harvested from the patient’s blood by doctors during the study. Endothelial nitric oxide synthase (eNOS) is a gene that is loaded into the cells. These extra copies genetically alter the cells. Maintaining healthy blood vessels is impossible without the gene eNOS. Doctors re-inject the cells into the patient after they have been genetically modified and grown in the lab. The hope is that the damage that has occurred in the patient’s lung’s blood vessels will be reversed by the treatment.

“It’s a very, very novel and first in the world application of this technology. This will be very exciting if we can halt the progression of the disease … we’re hoping we can, in fact, reverse the disease in many cases,” Kutryk said.

Treatment is being administered with increasing doses given to subsequent patients as the study is still in the early phases of testing.

“We’re certainly seeing positive results at the moment, but we expect to see much better results as we increase the doses of genetically modified cells,” Kutryk said.

The study is currently ongoing in Toronto and Montreal.

According to a study published recently in the Proceedings of the National Academy of Sciences (PNAS), researchers have discovered a key protein that controls how stem cells “choose” to become smooth muscle cells that support blood vessels or skeletal muscle cells that move limbs. The results may point in the direction of new treatments for diseases that involve the creation of new blood vessels from stem cell reserves that would otherwise replace worn out skeletal muscle in addition to providing insight into the development of muscle types in the human fetus. New treatments could also be developed for cancer and atherosclerosis.

Physician researchers should start watching to see if a previously undetected side effect exists since the newly discovered mechanism also suggests that some current cancer treatments may weaken muscle.

With as many as 400 cell types in millions of combinations, humans develop from a single cell into a complex being thanks to stem cells. The potential to develop into every kind of human cell is locked within the fertilized embryo, or original single human cell. As we develop in the womb, successive generations of stem cells specialize (differentiate), with each group able to become fewer and fewer cell types.

The ability to become smooth muscle, skeletal muscle, blood, or bone is a characteristic of a set of mostly differentiated stem cells. Ready to differentiate into replacement parts depending on the stimuli they receive, many human tissues keep a reserve of stem cells on hand in adulthood. The stem cells take the required route if the body signals that skeletal muscle needs replacing. The same stem cells may become smooth muscle that supports the lining of blood vessels if tissues signal for more blood vessels.

A transcription factor called Myocardin may be the master regulator of whether stem cells become skeletal or smooth muscle. The discovery was made by a team of collaborating researchers at the University of Texas Southwestern Medical Center, and the Aab Cardiovascular Research Institute at the University of Rochester School of Medicine & Dentistry. Myocardin is a transcription factor, a protein designed to associate with a section of the DNA code, and to turn the expression of that gene on or off. Smooth muscle cells were originally thought to be the only tissue affected by Myocardin which was believed to be a protein that promoted cell growth by turning regulatory genes on. Myocardin is shown to also turn off genes that make skeletal muscle in the PNAS report.

“These findings could eventually lead to stem-cell based therapies where researchers take control of what the stem cell does once implanted through the action of transcription factors like myocardin, unlike current therapies that “hope” the stem cell will take a correct differentiation path to fight disease,” said Joseph M. Miano, Ph.D., senior author of the paper and associate professor within the Aab Cardiovascular Research Institute at the University of Rochester Medical Center “More specifically, many diseases are driven by whether stem cells decide to become skeletal muscle, or instead to become part of new blood vessel formation. These discoveries have created a new wing of medical research that seeks to understand the genetic signals that turn on such stem cell replacement programs.”

Atherosclerosis, or hardening of the arteries, for instance, becomes likely to cause heart attack or stroke when cholesterol-driven plaques that build up inside of arteries become fragile. Tissue death occurs when clots that block arteries develop from these plaques interact with circulating factors due to arterial rupture. In theory, the plaques could be strengthened to prevent rupture by injecting stem cells programmed to become smooth muscle said Miano.

Conversely, in order to grow, tumors must be able to grow blood vessels. New blood vessels are built by turning on vascular endothelial growth factor (VEGF), the tumor accomplishes this by sending signals for stem cells to form smooth muscle in combination with other signals.

Would manipulating myocardin along with VEGF interfere with tumor growth by cutting off its blood supply?

Do current VEGF-based treatments kick myocardin into action, creating smooth muscle instead of continually repairing worn out skeletal muscle?

Since VEGF is used experimentally to treat peripheral artery disease and coronary artery disease, is this treatment reducing the skeletal muscle strength of these patients?

Miano’s team found that myocardin is a bi-functional developmental switch with the ability to both turn off the genes that turn stem cells into skeletal muscle as well as turn on a set of genes that turns stem cells into smooth muscle. Providing the biological context that made sense of Miano’s finding was accomplished by applying the same idea to the development of the fetus via transgenic mouse studies by the team at Southwestern.

A group of cells in the human fetus known to develop into skeletal muscle are know as the somite. This has been the focus of research at many institutions. Myocardin is expressed briefly in the somite during development in mice, but then disappears from that region of the fetus. This was determined during cell lineage and tracking studies performed by the Southwestern team. This current data leads to the surprising theory that both skeletal and smooth muscle cells come from the same stem cell region. To make the new human’s supply of smooth muscle cells, Myocardin briefly switches on. Blood vessels are formed when the cells migrate to another area. Then allowing the somite to continue differentiating into skeletal muscle, Myocardin quickly shuts off. Skeletal muscle would not develop properly if the turn off did not occur.

Seeking to define ancient sections of our genetic code that may soon be as important to medical science as genes has been the focus of many teams including Miano’s in recent years. How small regulatory DNA sequences tell genes where, when and to what degree to “turn on” in combination with enzymes that seek them out has been the concern of this new wave of research. This is in contrast to putting the spotlight on on how genes work.

The workhorses that make up the body’s organs and carry its signals; genes are the chains of deoxyribonucleic acids (DNA) that encode instructions for the building of proteins. The potential to create new classes of treatment for nerve disorders and heart failure are a side effect of the growing knowledge of how regulatory sequences control gene behavior. Once thought of as “junk DNA”, regulatory sequences are emerging as an important part of the non-gene majority of human genetic material. The complete set of DNA sequences that regulate the precise turning on and off of genes is referred to as theregulome and it’s study presents a new frontier in genetic research.

In an article by Miano and team published February 2006 in the journal Genome Research, they described one such regulatory sequence: the CArG box. The nucleotide building blocks of DNA chains may contain any one of four nucleobases: adenine (A), thymine (T), guanine (G) and cytosine (C). Any sequence of code starting with 2 Cs, followed by any combination of 6 As or Ts, and ending in 2 Gs is a CArG box.

Occurring approximately three million times throughout the human DNA blueprint, all together there are 1,216 variations of CArG box according to Miano. CArG boxes exert their influence over genes because they are “shaped” to partner with a nuclear protein called serum response factor (SRF) and several other proteins within a genetic regulatory network, including Myocardin. As many as sixty genes so far have been found to be influenced by the CArG-SRF, including many involved in heart cell and blood vessel function.

Past studies had determined that myocardin is a co-factor with SRF in CArG-Box mediated genetic regulation of stem cells. Through CArG box interaction, researchers believed myocardin partnered with SRF to turn on smooth muscle genes until now. But serving as a potent silencer of gene expression for the stem cell to skeletal muscle gene program, the current findings suggest that myocardin has a second role, independent of its partnership with CARG-SRF.

“With its dual action, myocardin is an early example of the efficiency and elegance of the system of genetic controls, where one factor has more than one complementary effect on the development of the body,” said Eric Olson, Ph.D., chair of the Department of Molecular Biology at the University of Texas Southwestern Medical Center in Dallas, and also senior author of the study.

To investigate if blood flow can be restored to the heart by promoting new blood vessels to grow, University of Florida researchers are planning to test a therapy in which stem cells are injected into the hearts of people with daily chest pain and severe coronary artery disease.

Procedures such as bypass surgery or angioplasty were ineffective on these particular patients. Traditional medications also failed to restore blood flow to the hearts of these individuals.

“The general idea is that by providing these cells of blood vessel origin, we hope to either generate new blood vessels from the growth of these implanted cells or stimulate the heart to regenerate new blood vessels from the cells that reside in it,” Carl J. Pepine, lead author of the study, M.D., chief of cardiovascular medicine at UF’s College of Medicine said.

“It’s not completely clear whether it’s the actual cell itself that would do this or whether it’s just the milieu and the chemical signals that occur from the cells that would result in this,” he said.

The forthcoming double blind, placebo-controlled study is known as the Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia Trial, or ACT34-CMI.

Chronic reductions in blood flow to the heart will be investigated. Particularly, the effectiveness and safety of using a patient’s own stem cells to treat this condition will be the focus of the study. 15 patients are enrolled to determine if the treatment will improve symptoms and long-term outcomes.

Exercise tolerance, improvements in quality of life, and whether or not the heart function improves will all be part of the evaluation.

The study involves a number of screening tests, followed by stem cells extraction. In order for stem cell collection to occur, a series of protein injections are administered to the patients that promote the stem cells release from be bone marrow, and into the peripheral blood.

During a procedure called apheresis, the stem cells which are called CD34+ stem cells, are harvested from the patient. Theses cells help stimulate blood vessel growth said Chris Cogle, an assistant professor of medicine at the UF’s College of Medicine Program in Stem Cell Biology and Regenerative Medicine.

A placebo, or one of two different dosing levels of stem cells will be randomly administered to each respective patient.

“Physicians will use a catheter-based electrical mapping system to find muscle they think is still viable but not functioning,” said R. David Anderson, an associate professor of medicine at UF and director of interventional cardiology.

Over the course of a year following the procedure, patients will be periodically evaluated by magnetic resonance imaging and echocardiography.

One trial focuses on patients with congestive heart failure or chronic chest pain that has not responded to traditional treatment, the second trial focuses on patients who have had a heart attack within a week preceding study enrollment, and the third focuses on patients whose heart attack occurred within the preceding two to three weeks.

The life of a New York woman was almost destroyed because of a root canal treatment that became infected. Once an active individual, the infection spread causing Ann to have difficulty breathing as the bacteria multiplied and spread towards her heart. Her heart began to fail when one of her heart valves stopped functioning properly.

Ann was rushed to have immediate valve repair once the doctors found the source of the problem which was initially mistaken for pneumonia. She grew sick of being tired all the time as the months following surgery became a struggle.

A company in Bangkok, Thailand was reporting success using a patient’s own adult stem cells to treat cardiomyopathy, ischemic heart disease, and congestive heart failure. The woman investigated further, intrigued by the possibility of getting her life back. Ann had made up her mind to the extent of 50/50, but the tipping point came when over Thanksgiving, she couldn’t pick up her grandson.

The condition of “heart muscle disease” is often referred to as cardiomyopathy. Often leading to heart failure or sudden death, it occurs in both women and men. Cardiomyopathy is also a term describing a series of disorders causing primary heart muscle dysfunction. There is no known cure for this condition, of which the most common form causes 10,000 deaths each year in the United States.

Now adult stem cells may be the treatment answer for this condition. A Bangkok, Thailand, based company claims to have developed a treatment for dilated cardiomyopathy. Patients are typically characterized by low energy, pain, restricted activity, brevity, and cost. But patients can travel to Bangkok to for stem cell treatment and possibly leave the aforementioned symptoms behind.

A Michigan man named Jason is perhaps the clinics biggest success.

By the time Jason was 15, he had a pacemaker. By 21 he was diagnosed as having cardiomyopathy and by 25 he had a defibrillator in place and an ejection fraction of just 8-10 percent. Jason was born with an atrial septal defect. Now 34, Jason calls himself lucky. Adult stem cell therapy freed him from the domination and restrictions of heart failure. He says he feels so much better that if he started training, he thinks he could do a triathlon.

As he was removed from a heart transplant list, his mother searched for help. As he went back and forth to specialists having his medications reviewed, since that is all he was left with. He constantly felt depressed and tired since some of the medications had unpleasant side-effects. Then his mother found the stem cell clinic. After being examined by Dr. Patel from the University of Pittsburgh, he was on his way to Bangkok. Dr. Patel felt that adult stem cells could help Jason.

A small amount of blood was withdrawn from Jason once he arrived in Bangkok. Stem cells were harvested from the blood and injected directly into his heart muscle at the Bangkok Heart Hospital. Jason knew his life was changing only a short month later.

“My heart was beating better, more rhythmically, and I had more energy,” he said. “After six months I was up and flying, feeling 100 percent different. I could mow the lawns, take walks, ride a bike with my kids, lift weights — do whatever I liked,” he said. “I’m always on the go with our fifth child on the way and always busy as a full-time parent.”

Jason is very happy to spend time advising other cardiomyopathy sufferers of the power of positive thinking and he has always enjoyed a huge level of support from his family and friends.

“Always try to be positive,” he counsels. “There is hope. Take care of your diet and help get the word out that adult stem cell therapy is worth getting done. It’s nothing like what you would have thought.”

Jason talks to other patients about his treatment, which is not available in the United States, and explains what it is like to fly to Thailand and receive stem cell injections.

Continuing research is revealing encouraging clinical outcomes for adult stem cell use for the treatment of many different conditions. Soon, more patients will be aware of the option to travel abroad to Thailand as well as other countries for treatment. Those patients will know that skilled doctors in world-class hospitals can perform this procedure which is straightforward and effective; and that they cannot be harmed by a therapy that uses their own adult stem cells.

Using a person’s own bone marrow, doctors were able to grow new blood vessels. However, in order for patients with diseased arteries to benefit from the test-tube grown vessels, a few more years of research will be required said researchers. Still, the accomplishment is yet another large step for adult stem cells and demonstrative of their therapeutic potential.

“Our studies show that bone marrow is an excellent source of stem cells that can be coaxed into creating blood vessels,” Stelios Andreadis, associate professor in the University at Buffalo department of chemical and biological engineering, told United Press International.

Andreadis said that endothelial and smooth muscle cells make up the test tube created blood vessels.

“These stem cells can be used in regenerative medicine for cardiovascular applications,” he said.

Especially for those found in and around the heart, the main reason for creating new blood vessels is for use in arteries said Andreadis. However, the blood vessels created in his laboratory are capable of being used, at the very least as, veins in humans right now.

The new blood vessels should be engineered to withstand internal pressures as high as 1,200 millimeters of mercury in order to have the strength to be used to replace diseased coronary arteries. This is 10 times above the normal limit. Having a top strength of about 200 mmHg, bone marrow stem cell derived blood vessels are not yet strong enough.

“We need to improve the matrix around which the cells grow in order to have strong enough blood vessels for replacing human arteries,” he said. The researchers have already used tissue engineered vessels in animals such as sheep with good results, he said.

Cardiovascular Research recently published Andreadis’ preliminary work. Providing a desirable alternative to the venous grafts now routinely done in patients undergoing coronary bypass operations, the paper demonstrated the potential for eventually growing tissue-engineered vessels out of stem cells harvested from the patients who need them.

A high 10-year failure rate, discomfort and pain at the donor site, and the limited availability of vessels are some of the disadvantages of venous grafts.

Using a tissue-specific promoter for alpha-actin (a protein found in muscles that is responsible for their ability to relax and contract) in conjunction with a fluorescent marker protein, Andreadis reported on a novel method for isolating functional smooth muscle cells from bone marrow.

One of the most important properties of blood vessels is their ability to proliferate and the ability to contract in response to vasoconstrictors. In their expression of several smooth muscle cell proteins, the tissue-engineered vessels performed similarly to native blood vessels.

Critical to the functioning of artificial blood vessels, both elastin and collagen are produced by the vessels. These components also give tissue their elasticity and strength.

The John R. Oishei Foundation of Buffalo and the Integrative Research and Creative Activities Fund in the Office of the Vice President for Research at the University at Buffalo, part of the State University of New York funded Andreadis’ research.

“The work in Buffalo shows the promise that stem cells have in their ability to produce different structures,” said S. Chiu Wong, associate professor of medicine at the Weill Medical College at Cornell University. “This pre-clinical work shows again that stem cells can be a rich source for development. It certainly remains a fruitful area of research.”

Working on producing more coronary blood vessels is another aspect of stem cell research which Wong and his colleagues are working on. In an attempt to generate blood vessel growth, stem cells are injected directly into heart muscle. Wong and his team are part of a multicenter clinical trial involved to this particular study which has been funded by Baxter.

A leading cardiologist is saying that the treatment of heart disease has been revolutionized by the concept of “growing” heart muscle and vascular tissue and manipulating the myocardial cellular environment by using stem cell therapy.

City-based Harvey Super Specialties Hospital Chairman M P Naresh Kumar told reporters that adult stem cells harvested from peripheral blood or bone marrow are capable of replicating, differentiating and promoting heart muscle (myocardial) repair.

He said that recently, adult stem cells have proven themselves to have great therapeutic benefit and clinical relevance for the treatment of heart disease, even though there is still experimental work that must be completed.

Severe heart disease cases that have been treated successfully with adult blood stem cell infusions were cited as examples of recent stem cell success by Kumar. Once such example involved a 53-year-old woman. After all other treatments proved to yield no benefit, the woman, who also suffered from diabetes and high blood pressure was treated using adult stem cells.

A heart transplant was out of the question for her and beyond her means. Her ejection fraction had dropped to 35 percent and she had severe heart failure. Diagnosed with dilated cardiomyopathy, she underwent stem cell therapy as last resort.

Upon discharge following cell therapy, her ejection fraction had already increased to 49 percent. She was infused using a catheter technique via a coronary route.

The accessibility, safety, feasibility, and cost effectiveness, of stem cell therapy was pointed out by Kumar.

He remarked that the treatment cost a relatively small sum of Rs 25,000 (about $610 dollars), where if the treatment had been performed in the United States it would have cost about Rs 40 lakh.