Cardiac Stem Cell Therapy Comes Closer to Mainstream

In the therapeutic efforts that have been directed at the treatment of a variety of cardiac disorders, a great deal of progress has been made in the understanding of this science since the year 2000. Many questions still remain and research directed at answering some of these questions was presented in the current issue of CELL TRANSPLANTATION (Vol.16 No. 9), The Proceedings of the Third Annual Conference on Cell Therapy for Cardiovascular Disease. The issue was comprised of eleven separate papers, four of which are sampled below.

Amit N. Patel, MD, MS, director of cardiac cell therapy at the University of Pittsburgh Medical Center and lead author of an overview and introductory article, Cardiac Stem Cell Therapy from Bench to Bedside, stated that

MS and ALS Adult Stem Cell Progress Made in Israel

By injecting sufferers of neurological diseases with therapeutic quantities of cultured adult stem cells, scientists based at Jerusalem’s Hadassah University Hospital have broken new ground in the field of stem cell research.

The researchers extracted stem cells from the hip bone marrow of 26 multiple sclerosis (MS) and amytrophic lateral sclerosis (ALS) patients. The cells were re-injected into the patients via lumbar puncture following a two-month long process of in vitro cleansing, multiplication and chemical ‘tagging’. The researcher team was led by Professor Dimitrious Karussis and Prof. Shimon Slavin, the recently retired head of Hadassah’s bone marrow unit.

The particular type of stem cell used in the trial, marked a world first according to Karussis.

“The sole aim of this study was to explore the feasibility and the safety of this treatment, since it is applied for first time,” Karussis told ISRAEL21c.

The experiment was deemed a success with no adverse effects reported. Leading the way for further developments in forthcoming clinical trials, it was encouraging that patients also displayed anecdotal improvements in clinical symptoms.

“Most MS patients reported a stabilization of their condition and some an improvement in function, especially in sphincter control, muscle power in arms, tremor and stability in walking,” Karussis said. “ALS patients continued to show signs of deterioration – though at a lesser than previous degree.”

This is good news for both groups of patients. Resulting in impaired sensory, motor, balance and vision function, MS causes damage to the body’s central nervous system and affects over 2.5 million people worldwide. Causing the gradual and fatal loss of the patient’s capacity for movement, ALS or Lou Gehrig’s disease, involves a similar degeneration of neuronal cells. ALS is more rare and progresses more rapidly.

Both conditions are ideal targets for stem cell treatment since they are both caused by the deterioration of a specific type of cell.

Suggesting that it might be possible to regenerate damaged nervous systems through cell re-growth, the Hadassah researchers found that transplanted adult stem cells began to differentiate into the kinds of cells which the diseases had destroyed. This was observed during extensive experimentation on animal models of MS and ALS.

Despite suffering from a similar motor neuron disorder, the treated lab mice retained 90 percent of their neurons after the equivalent of one or two years in the human progression of the diseases.

Marking the first time such adult stem cells have been injected into human patients, Karussis cited the most recent safety study. The study has paved the way for a larger efficacy trial to be held over the course of the next few years, despite remaining highly experimental since the small-scale study lacked a control group.

“We are encouraged as these are patients with advanced cases, many of them in wheelchairs,” Karussis told the Jerusalem Post.

Since most of the attention in recent years has been directed towards embryonic stem cell research, the current work utilizing adult stem cells is significant say scientists. There are advantages to using adult cells. The chances of immune rejection are significantly reduced since the patient can serve as his or her own donor. The ethical issues which surround embryonic stem cells is also avoided with this approach.

The researchers hope to launch a controlled clinical trial of the therapies after first enlarging the safety study to include more patients. Applications from potential trial patients are a welcome sight.

However, a license must first be obtained from the Ministry of Health, as well as funding to cover the expense of treating patients; a cost that can be up to $20,000 per patient. Despite these significant challenges, the team says it will all be worthwhile in the long run.

Stem cells, Karussis notes, “have already shown some promise in the treatment of joint and bone diseases, immune conditions and ischemia of the heart.” And he is optimistic, he says, that MS and ALS will join that auspicious list one day “not far into the future.”

Ethical Bio-Replacements on the Way Thanks to Adult Stem Cell Breakthroughs

Following in the footsteps of their Japanese and U.S. colleagues, another team of U.S. scientists has come up with a way to produce

Stem Cell Research Grant Awarded by Archdiocese

A team of researchers investigating the potential of adult stem cells has been awarded with a $100,000 grant by the Archdiocese of Sydney announced Cardinal George Pell.

The potential for stem cells derived from human dental pulp to transform into neuron cells will be investigated by the researchers who are based in Adelaide. The cells could be used to treat stroke victims if they can be effectively transformed.

Dr. Simon Koblar of the Australian Research Council Center for the Molecular Genetics of Development at the University of Adelaide and Associate Professor Stan Gronthos of the Hanson Institute led the research team. Instrumental in advancing their studies, was PhD. student Dr. Agnieszka Arthur, whom both the researchers praised. Dr. Arthur is doing postdoctoral work at the Hanson Institute and is a co-investigator of the grant.

Expansion of Cord Blood Stem Cells a Valuable Tool

Immediately following birth is the only time cord blood cells can be collected. This means that the number of genetically unique cord blood stem cells is limited to the quantity obtained at this single point in time. Researchers are developing methods to stimulate stem cells to divide and increase in number while retaining their primitive state to allow for multiple uses and also to increase their capacity for transplantation in adolescents and adults. The process is called stem cell expansion.

For the patient to use their own cord blood samples for more than one treatment as well as improve transplant outcomes, stem cell expansion is an important tool. The science of using the body’s own cells to repair or replace damaged tissues and organs is refered to as regenerative medicine. And stem cell expansion is important to the advances in this field, which will likely increase the number of diseases that cord blood stem cells are able to treat as a result.

Several expansion studies and clinical trials are underway, even though expanded stem cells are not yet approved for medical use in humans. One or many of the methods will eventually be available with an emerging number of expansion techniques succeeding in vitro and in animal models.

In fact, successful and reproducible results can be achieved in cord blood stem cell expansion as indicated in published research. In one study, the number of stem cells in culture were expanded 389-fold using isolated primitive embryonic-like stem cells from cord blood. In another study, researchers isolated stem cells from cord blood using cell surface markers and expanded the number of stem cells in culture up to 723-fold.

More than 6,000 men, women and children are searching the NMDP registry on any given day according to the National Marrow Donor Program (NMDP). Even more patients, including adults could be treated by expanding the volume of stem cells available in a cord blood unit. Families who initially opted for private banking could use their cord blood stem cells for multiple treatments, this could potentially facilitate the donation of a portion of their cord blood sample to patients in need.

A number of clinical trials are currently being conducted to evaluate the use of expanded cord blood stem cells in humans.

In an international multi-centered trial, the first patient received a transplant of stem/progenitor cord blood stem cells in combination with non-expanded cells from the same unit in November. For hematological malignancies, including leukemia, and lymphoma, the trial will assess the safety and efficacy of expanded cord blood transplantation as a treatment.

The applicability of stem cell expansion in human cord blood transplants is being evaluated in other trials as well. Three such trials have been noted below.

-27 patients with malignant and nonmalignant disorders werte treated using expanded cord blood stem cells by investigators at Duke University Medical Center. The patients demonstrated the safety of this cell expansion technique for clinical use and exhibited durable long-term engraftment.

-The promising role cell expansion may hold in adult transplantation was demonstrated in another trial involving two adults with chronic myelogenous leukemia. Rapid engraftment was observed after receiving expanded cord blood transplants in the two patients at Hackensack University Medical Center in Hackensack, New Jersey.

-Another trial demonstrates the feasibility and safety of treating patients with high-risk malignancies using expanded cord blood stem cells. In a study at the University of Colorado, thirty-seven patients with blood or breast cancer received expanded cord blood transplants.

An indication of the scientific importance of stem cell expansion is made clear by the increasing number of institutions that are actively pursuing these new technologies. Expansion technologies may be available to more patients in the future given the positive results seen in studies thus far.

New Characteristics of Nanog Stem Cells Revealed

Aiding the understanding of how stem cells can be used to treat disease and injury, researchers at Edinburgh University have made new discoveries about stem cells.

Previously thought to operate like an on/off switch for duplication, the findings focus on the nanog stem cell.

But the cells actually control the efficiency with which stem cells duplicate according to findings by scientists at Edinburgh University. Nanog operates like a dimmer switch.

For use in medicine, the findings give scientists greater control over stem cell behavior.

Key Blood Cell Isolated by Stanford Researchers

A finding that may lead to more effective treatment of leukemia and other blood diseases, Stanford University researchers have isolated a human blood cell that represents the “great grandparent” of all blood cells.

The cell gives rise to all other cells of the blood since it is the first offspring of blood-forming stem cells that reside in bone marrow. The cell itself is called the multi-potent progenitor.

Never before isolated in humans, the multi-potent progenitor was previously well-known in mice.

The research was performed by Dr. Irving Weissman, director of the Stanford Institute for Stem Cell Research and Regenerative Biology, co-lead author Dr. Ravindra Majeti, an instructor in hematology, and co-lead author Dr. Christopher Park, an instructor in pathology.

“We can compare the leukemic stem cell to this progenitor cell and from that find out what makes the leukemic stem cell different,” Weissman said, which could lead to new treatments for leukemia patients.

28 Heart Failure Patients Treated with Adult Stem Cells

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.”

Breast Reconstruction with Fat Stem Cells

Doctors repaired breast defects in women who have had cancerous lumps removed by using stem cells from liposuctioned fat for the first time.

After cancer surgery, women are often left with cratered areas of the breast. Although the approach is still in experimental stages, millions of women now have hope in correcting post breast cancer surgery deformities. Without using artificial implants, women who desire breast augmentation surgery could also benefit from the technique.

Doctors in the United States consider the procedure to have great potential, despite the fact that it has been tested on only two dozen women in Japan so far.

“This is a pretty exciting topic right now in plastic surgery,” said Dr. Karol Gutowski of the University of Wisconsin-Madison. “There are people all over the country working on this.”

Larger studies are in the works, and they should take place in Japan and Europe next year. The initial Japanese study was reported Saturday at the San Antonio Breast Cancer Symposium.

Each year in the United States, more than 100,000 women have lumps removed from their breasts. Taking the entire breast, mastectomies are sometimes necessary, but lumpectomies are often the procedure of choice. However, as much as a third of a woman’s breast may still be removed, and what’s left is often deformity.

“It’s almost a euphemism” to call it a lumpectomy, said Dr. Sydney Coleman, a plastic surgeon at New York University who is interested in the stem cell approach.

Dr. Sameer Patel, a reconstructive surgeon at Fox Chase Cancer Center in Philadelphia, said that the defect “initially may not be as noticeable”. However, he was quick to point out that the result often worsens, especially if the woman undergoes radiation treatment.

“There’s a growing push to try to involve the plastic surgeon particularly for this reason — to try to avoid a defect,” but once one develops, options to repair it are limited, Patel said.

Odd-shaped deformities from radiation or lumpectomies cannot be repaired properly with the implants that are sold today. They are not designed to repair this type of damage.

“Each one is so different, there’s no little thing you can just pop in there,” Gutowski explained.

Rearranging tissue to more evenly distribute what’s left, transplanting a back muscle to boost the flawed breast, or attempting to make the opposite breast smaller in order to match better are all current methods that are used by doctors to remedy the problem. But these procedures involve surgery and leave scars.

Often dieing and turning hard and lumpy, or getting reabsorbed into the body, mini implants of fat tissue have been attempted. Interest in the use of fat cells has been renewed with the recent discovery that fat cells are rich in stem cells — master cells that can replenish themselves and form other tissues in the body.

From the thighs, hips, or tummies of 21 breast cancer patients, doctors liposuctioned fat in the Japanese study. Half was processed to extract stem cells, and the other half was reserved as the main implant material and combined with the extracted stem cells following extraction. The fat/stem cell mixture was injected in three locations around the breast defect.

Doctors believe the stem cells will form lasting mini implants and keep the tissue from dying.

Dr. Keizo Sugimachi of Kyushu University in Fukuoka, Japan said that “about 80 percent of the patients are satisfied” with the results eight months after the procedure.

At one and six months after treatment, was a statistically significant improvement in breast tissue thickness.

The potential for cosmetic breast augmentation of healthy breasts is there, but the goal is to help cancer patients with their unmet medical needs first said Dr. Mark Hedrick.

The treatment is expected to cost $3,000 to $5,000.

Doctors must be cautious about using fat cells for cosmetic purposes until more is known says The American Society of Plastic Surgeons.

Gutowski heads a task force the society formed to study the science. Coleman is a member.

“It’s got great potential not only for breast but other cosmetic and reconstructive purposes,” like filling in facial defects from cancer or trauma, Gutowski said. “Imagine the aging face.”

More women may choose lumpectomies with the rise of better cosmetic treatments. Younger women in particular have opted for mastectomies because they are concerned about being left with a defect.

Now left with mismatched breasts Laurie Rapp was only 32 when she had a lumpectomy.

“One is so much smaller than the other one,” said the now 48-year-old restaurant manager in Philadelphia. “There’s quite a bit of puckering, and as I’m getting older I feel it’s getting worse.”

If the procedure would have been available when she had her surgery, she would have opted for the stem cells, but probably wouldn’t try it now.

“I definitely would have, especially because I wasn’t even married then,” she said.

Historic Spinal Surgery for Teen in Arizona

Finishing book reports and other homework may seem daunting to most 14-year-old boys. But when Matthew Baremore woke up and finished his assignments on Tuesday morning, the school work was cake compared to the medical history he made.

Matthew has scoliosis, and using a concentrated cocktail of his own stem cells and those donated from bone, he became the first in the state to undergo spinal fusion surgery.

New bone growth is facilitated by the stem cell technology and healing is also accelerated. The process of harvesting a piece of Matthews bone, which involves a second procedure, is also avoided with this method.

“Right now he has a fairly large bump on his back (and) his rib cage is being forced out of position,” Matthew’s mother, Becky, said as she ran her hand along his back.

With the potential to eventually interfere with Matthews breathing, the 50 percent curvature would have likely worsened if left untreated. That would result in a serious modification in his life, one that involves a passion for playing basketball.

Bone marrow was harvested from the teen’s pelvic bones by Dr. Mark Flood, a pediatric spine surgeon, at Banner Desert Children’s Hospital. The procedure took approximately four hours. Using centrifuge technology patented by an Austin, Texas firm, stem cells were extracted from the marrow.

Flood straightened and bolstered Matthew’s spine with a series of rods and pins _ a typical surgical treatment for severe scoliosis.

Crushed bone marrow from the hospital bone bank was combined with Matthew’s own stem cells which had been concentrated to 10 times the levels normal with traditional methods.

Between the rods, the puttylike mixture was injected into the upper-middle section of Matthew’s spine. The spine will be protected against further curvature with the mixture growing into bone in the injected location.

“What’s revolutionary is the use of the concentrated stem cells,” Flood said before the surgery. “We can avoid the pain of taking bone, and increase fusion.”

There is no cure for Scoliosis. The condition affects about two to three percent of the population and results in the spine curving in an “S” shape from side to side.

Curvatures of 25 to 40 degrees in adults and children may require a back brace, however, most individuals require no treatment. If the curve is more severe or the brace fails to correct the problem, surgery is recommended.

Until now, the surgical option usually required a bone graft, a second surgery and longer recovery.

Often diagnosed between the ages of 10 and 14, scoliosis can develop gradually. As Matthew hit puberty, he quickly grew to 6-foot-1, marking a fast development in his scoliosis. During a physical exam last spring, his condition was first noted.

Matthew was looking forward to getting the procedure over with on Tuesday. The eighth-grader and his twin brother Jordan, may have been a bit camera shy as well, with a media entourage following them around in the hospital.

Matthew’s strong bones made the procedure a bit more challenging, but Flood said that the surgery was a success.

“Everything went fine. Now it’s up to him to get through these next few days,” he said.

Matthew will return to school at Villa Montessori in Phoenix after a four to five day recovery stay in the hospital. He must wait at least one year before he can play basketball again, but rehabilitation therapy will start in about six weeks to improve strength and flexibility in his muscles.

“He’ll bounce back quickly,” Flood said. “That’s how kids are.”