For many patients who have run out of options, a new treatment could offer new hope.

The treatment is for patients who have had stents, surgeries, and other treatments without success. These patients suffer from severe coronary artery disease and are at great risk for heart attacks and progressive heart failure.

An injection of stem cells being tested by doctors at Chicago’s Rush University Medical Center with the hope that it will alleviate the problems patients have with their hearts.

Medical history may be made by James Campbell. The sixty-eight year old heart patient has volunteered to have an injection administered directly into his heart. The injection will be blind, meaning that he could possibly be injected with a placebo. But hopefully, the injection will be a special type of stem cell. Campbell is participating in a clinical trial to see if new blood vessels can be grown with stem cells.

“If it works, it’s worth it,” Campbell said.

“The hope is that these endothelial progenitor cells will grow and divide and allow and facilitate new blood vessels to enter that region of the heart muscle that’s not getting enough blood and oxygen,” said Dr. Gary Schaer, director of cardiac catherization at Rush.

Campbell wants to end the debilitating and chronic chest pain he has suffered for three years. He has survived through a heart attack and two heart surgeries already.

“I can walk maybe 60 to 65 feet and I start having chest pains,” Campbell said.

The day before the injection, Campbell donated his own stem cells like every other patient also enrolled in the trial.

“The advantage of the patient’s own stem cells is there’s no chance of rejection,” Schaer said.

Dr. Schaer says the no ethical issues come into play for this treatment. Several dozen patients like Campbell have been injected by Dr. Schaer using 3-D computer mapping and sophisticated catheter technology since the trial started. The results have been incredibly encouraging and there have been no adverse reactions.

“The patients that we’re seeing in follow up, and we’ve seen several that have come back for their one year follow up, we’ve seen marked improvements in their symptoms,” Schaer said.

The current trial is still recruiting patients. But Rush Medical has more trials planned, with different diseases and different kinds of stem cells.

Some of Campbell’s hobbies prior to his heart problems were riding motorcycles and canoing. He is hoping that the injections will alleviate his pain, and allow him to go back to a normal life where he can be active again.

The FDA approved clinical trials for adult stem cells to the tune of 1100 in 2006. But 2007 was even more successful for adult stem cells. Over 1400 FDA approved trials for 73 different conditions in humans where patient health has been improved through adult stem cell therapy were documented in peer-reviewed studies in 2007.

Umbilical cord blood, placentas, and other tissues in the body contain adult stem cells. They are found throughout the entire body. No embryos are destroyed when extracting adult stem cells, which is in contrast with the extraction of embryonic stem cells.

We have decided to publish a yearly update each fall/winter since treatments with adult stem cells are continually increasing and continue to be impressive. (Note: Embryonic stem cells have never produced successful treatment trials in humans.)

Adult stem cells do not create tumors, unlike embryonic stem cells.

The research and treatments involving adult stem cells has been fast paced since our 2006 paper, thus, we have summarized some of the developments in the field below.

The Regeneration of Heart Tissue

Eight years ago, Doug Rice was diagnosed with congestive heart failure. Due to his diabetes, he was unable to get a heart transplant.

Rice decided to travel offshore for adult stem cell treatment since he was facing fatal heart failure. Stem cells were extracted from a sample of blood taken from Rice. The cells were differentiated into angiogenic cell precursors, then transplanted into Rice’s heart.

The results were immediate for Rice, who experienced an increase in his hearts efficiency of 30 percent. He originally had an ejection fraction of 11 percent.

According to Rice, “I’ve been around a lot of people with bad hearts. I know if they looked at [adult stem cell therapy], it might save their lives. I firmly believe it saved mine.”

A few other companies have developed adult stem cell technology for heart patients.

Marc Penn, director of the Bakken Heart Brain Institute at the Cleveland Clinic, says of one new therapy, “It’s very exciting, perhaps a sea-changing trial for the field … offering the chance of an off-the-shelf-product.”

Bone marrow stem cells have been used by Bodo-Eckehard Strauer to treat over 300 heart patients. He is the director of the cardiology department at Dusseldorf University Hospital. A patient who was

Using autologous stem cells, 28 patients were recently treated for acute myocardial infarction (MI) at the Sir Hurkisondas Nurrotumdas (HN) Hospital in Mumbai, India. The Medical Research Society of HN Hospitals funded the research. Patients from the 39-68 years age group were chosen for the project which was started in June of 2005.

“Most attempts including ours have considered the adult bone marrow as the source of the repair stem cells which is a source of hematopoietic and stromal stem/progenitor cells and have demonstrated that the implantation procedure is safe, feasible and effective in terms of improving the myocardial salvage rate of the infarcted myocardium. The latter can be attributed to the angiogenic events or secretion of angiogenic cytokines by these cells,” said Dr. VK Shah, Principal Investigator and Interventional Cardiologist, HN Hospital.

Facilitating the ability of the heart to heal itself, patient’s own bone marrow stem cells reach the infarcted area with the blood supply and contribute to the restoration of stem cell niches. The patient’s cells are injected into the culprit coronary artery after the opening of the occlusion by primary angioplasty.

“All the cases were successful without any complications. This procedure is done while the patient is fully conscious,” Dr. Shah claimed.

Further explaining the process, Dr. Shah said, “We have completed clinical check-up of all the patients of two, four, six and twelve weeks. Further a six-month follow-up of left ventricular (LV) function assessment by LV angiography and cardiac magnetic resonance imaging in stem cell therapy group have demonstrated an increase in LV ejection fraction (EF) by 7-12 per cent as compared to 1-3.2 per cent controls. There is improvement in LV systolic function, wherein LV end systolic volume (LVESV) has decreased significantly to 16-28 per cent. No patient has demonstrated deterioration of regional wall motion or any other side effects during the follow-up period. The results of our study show favourable trend towards improvements of cardiac functions which is the key determinant for long-term survival.”

In order to see what the long term effects of bone marrow infusion on any organ are, the hospital has carried out some routine tests at the end of two years. Normal in all patients were; lipid profile, renal function tests, liver function test, chest X-ray, sonography of abdomen and blood tests which include complete haemogram, ECG, and 2D echocardiography. The detailed clinical evaluation was performed on all patients starting with the first who received bone marrow stem cell therapy.

“In addition to the regular clinical follow-up, these tests helped us in assessing the safety and feasibility of transfusing autologous bone marrow stem cells (ABMSC) into the culprit coronary artery after an acute anterior wall MI,” said Dr. Shah.

According to patient Rajaram Chandra Jagdale (54), who underwent the therapy last April after suffering from an acute MI, “I am doing fine after the therapy.”

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.