Growing Miracles

Medical experts have focused their attention on a civilian man in the U.S. who regrew his finger following an accident at his home. After slicing off the end of his finger in the propeller of a hobby shop airplane, Lee Spievack was treated with a powder which he calls “magic dust” and which was applied directly to the injured area. Within 4 weeks, Spievack, who is in his 60s, regrew the entire missing half-an-inch of his finger, which included not only flesh and blood vessels but also bone and nail. The regrown finger has minimal scarring and is once again whole and complete.

The “magic dust” is a medical powder known as “extracellular matrix”, which is derived from the bladders of pigs and which contains a mixture of protein and connective tissue. Surgeons often use this powder in the repair of simple tendon injuries. Now, however, this extracellular matrix is a key component of the new field known as regenerative medicine.

As Dr. Stephen Badylak at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh explains, this powder “tells the body to start that process of tissue regrowth.” Although the precise cellular mechanisms that are at work have not yet been fully elucidated, the extracellular matrix mobilizes the body’s naturally occurring stem cells, thereby stimulating the body’s natural regenerative abilities. According to Dr. Badylak, “It will change the body from thinking that it’s responding to inflammation and injury to thinking that it needs to regrow normal tissue.” When asked if this extracellular matrix could regenerate entire limbs, Dr. Badylak replies, “In theory, yes.”

A number of researchers are now putting this theory to the test. In conjunction with the University of Pittsburgh and in collaboration with Dr. Badylak, the U.S. Army is already applying such a potential therapy to wounded soldiers who are returning from the war in Iraq. Dr. Steven Wolf, at the Army Institute of Surgical Research in Texas, describes how the U.S. military has already invested millions of dollars in regenerative medicine, not only for amputees but also for burn victims. In related studies that are being conducted simultaneously in Europe, a device currently under development by German researchers is being used for spraying a patient’s own cells onto burn wounds, which signals the skin to regrow itself. In a newly developed upcoming surgical procedure, Dr. Badylak will implant the extracellular matrix material, which has been formed into the shape of an esophagus, into patients who are suffering from throat cancer. As he explains, “We fully expect that this material will cause the body to re-form normal esophageal tissue.” Similarly, this same extracellular matrix material has also been placed directly onto heart muscle, like a bandage, to help repair damaged tissue following a heart attack. Dr. Joon Sup Lee, one of the surgeons and researchers at the University of Pittsburgh Medical Center, has been injecting autologous stem cells directly into the hearts of patients in order to expedite recovery following myocardial infarctions.

According to Wyatt Andrews of CBS News, “researchers imagine a time when regrown limbs replace prosthetics, when regrown tissues replace surgery, and when the body does its healing with cells from within.”

Discovery of the Mechanism by which Stem Cells are Released from Bone Marrow has Vast Implications in Health and Disease

Researchers at Mt. Sinai Hospital in New York have identified the mechanisms that regulate the release of stem cells from bone marrow into the blood. It has long been known that bone marrow-derived stem cells regularly circulate throughout the blood, and many bone marrow transplantation procedures involve the harvesting of stem cells from the peripheral blood. Previously, however, the precise mechanisms by which the stem cells were released into the blood remained unknown. Dr. Paul Frenette and colleagues at the Mt. Sinai School of Medicine have now discovered that molecular adrenergic signals originating in the brain are sent via the sympathetic nervous system directly to “niches” within the bone marrow in which the stem cells reside, thereby triggering the release of the stem cells from these niches into the circulating blood.

The sympathetic nervous system is that part of the autonomic nervous system most commonly identified with the “fight or flight” response, but it is also highly sensitive to stress and is therefore easily activated by changes in circadian rhythms. All species exhibit circadian rhythms that are regulated by a biological “master clock” which in humans is anatomically located in the suprachiasmatic nucleus within the hypothalamus. External cues reset the biological clock daily, the most important one of which is light which stimulates highly photosensitive proteins in the photoreceptors of the retina of the eye from which signals are then transmitted across the retinohypothalamic tract to the suprachiasmatic nucleus which reinterprets the signals and retransmits them to the pineal gland where the hormone melatonin is secreted, and which is known to peak at night. From the hypothalamus through sympathetic nervous system pathways throughout the body, all physiological processes are regulated including cellular metabolism, hormone production, brain wave activity, body temperature, reproduction, and patterns of sleeping and eating, all of which are naturally entrained to the 24-hour cycle of the earth’s rotation.

In this particular study, the Mt. Sinai researchers used a mouse model in which the maximum release of stem cells from the bone marrow into the circulating blood was observed to occur during periods of rest, although changes in light and experimentally induced “jet lag” in the mice were found to alter the patterns of stem cell release. These results are the first to indicate a circadian regulatory relationship between the cyclical “biological clock” and naturally produced endogenous stem cells. The discovery holds many implications for the important role of these rhythmic oscillations in regenerative medicine and also in the natural regeneration that continually occurs in healthy individuals on a daily basis. In patients who need stem cell transplantation, for example, the collection of their own stem cells may be optimized by timing the harvesting of the cells to coincide with those peak hours of release. Additionally, the discovery also highlights the importance of maintaining regular sleeping habits, especially in today’s modern society, since the normal release of stem cells from the bone marrow into the circulating blood may be hindered by such factors as jet lag, sleep deprivation and other disruptions in natural circadian rhythms. The results of this study may offer one of the first concrete scientific explanations for the previously suspected correlation between night shift work and cancer, a causality which has been established by a number of previous studies and formally identified by the World Health Organization as well as by the International Agency for Research on Cancer, which in 2007 listed night shift work as “probably carcinogenic to humans.” A disruption in natural sleeping rhythms which in turn disrupt the peak release times of stem cells from bone marrow into the circulating blood could interfere with the body’s natural ability to repair itself daily and could therefore possibly also contribute to the formation of various types of cancer.

Grow Your Own Replacement Parts

In the U.S. alone, more than 98,000 people are currently on waiting lists for organ transplants. Demand greatly outnumbers supply, however, and many patients will die before ever receiving the needed organ. But now, stem cells offer an alternative solution.

Dr. Anthony Atala and his colleagues at the Wake Forest University in North Carolina believe that “anything inside the body can be grown outside the body.” So far they have already made 18 different types of body tissue from stem cells, which include heart valves and the entire heart of a mouse which was grown from scratch, layer by layer, as well as a new human bladder. Using Dr. Atala’s technique of growing an entirely new bladder, a patient in a clinical trial at the Thomas Jefferson Hospital in Philadelphia successfully received a new bladder transplant that was made from the patient’s own stem cells. It is believed that every tissue of the body contains its own stem cells, and in this particular case the bladder cells were isolated from the patient, expanded and, 8 weeks later, the new bladder was in the operating room and ready for transplantation. As Dr. Patrick Shenot, the transplant surgeon who performed the operation, explained, “It’s very much the future, but it’s today. We are doing this today.”

The research is already translating into big business. The biotech company Tengion, Inc., now exists almost exclusively for the “manufacture” of new bladders from a patient’s own stem cells. According to CBS news, “The Tengion Company has bought the license, built the factory, and is already making the bladders developed at Wake Forest.” According to Tengion’s CEO, Dr. Steven Nichtberger, “We’re actually building a very real business around a very real and compelling patient need. In regenerative medicine, I think it is similar to the semiconductor industry of the 1980s. You don’t know where it’s going to go, but you know it’s big.” Tengion has plans to expand beyond the creation of bladders, and to mass-produce blood vessels and kidneys.

Regenerative medicine is redefining most aspects of conventional medicine, and the field of organ transplantation is no exception. According to Wyatt Andrews of CBS News, “Patients in the future, instead of waiting years for a donated organ, will wait a few weeks and… grow their own.”

Australian Spinal Cord Research Could Bring New Hope

With the first Australian trial of a new adult stem cell treatment, the hope of improved movement for those with spinal cord injuries has been given a new boost.

In order to coordinate national and international research and apply it to patients, the new dedicated spinal cord laboratory at Melbourne’s St. Vincent’s Hospital. The facility is the first of it’s kind in Australia and will be the location where the trial is conducted.

With no cure in sight and the cost of care at an estimated $1.2 billion, Australia sees a new spinal cord injury every single day.

“This is a major unmet medical need,” said Dr. George Owen, head of Step Ahead Australia, (formerly the Spinal Cord Society of Australia).

After diving into a shallow pool 13 years ago, Dr. Owen’s son Sam became a quadriplegic. Sam is now 26 years old.

New leads into the treatment and possible cure for spinal cord injury may be developed during the trial where scientists will work with a spinal cord

Liver Repaired Using Experimental Stem Cell Drug

After doctors gave a man an experimental stem cell drug, the 20-year-old Abu Dhabi man’s liver repaired itself. He is now fully recovered.

A British scientific journal will publish the treatment results and recovery story of the man along with four others who underwent the same treatment with mixed results.

The man’s liver failed suddenly during treatment for leukemia tow years ago according Singapore based consultant general surgeon Dr. Susan Lim.

“He needed a liver transplant,” she said. “I treated him with the stem cell drug [which her team is studying] and within three days, he woke up,” she added.

After an evaluation by Dr. Lim, the man is considered to be fully recovered and tests show that his liver is functioning normally.

She said that

Stroke Damage Recovery with Adult Stem Cells

A faster and more full recovery is possible when stroke victims are treated with transplanted stem cells according to researchers in China, Canada, and Korea. The studies were conducted with bone marrow stem cells (BMSC) and human mesenchymal stem cells (hMSC).

The cells will travel to blood-deprived and damaged areas of the brain and help repair damage caused by stroke regardless of the site of injection. The two studies were both published in the most recent issue of the journal Cell Transplantation.

The subjects tested “exhibited significant reductions in scar size and cell death and improvements in neurological function when compared to controls that received no BMSCs,” said Ren-Ke Li, MD, PhD, who is the lead author of the joint Canadian-Chinese study.

Cell Transplantation associate editor Cesar V. Borlongan, Ph.D said that

Brittle Bone Disease and Stem Cells

Today an announcement was made that experiments on mice found they suffered fewer bone fractures following treatment with stem cells. Brittle bone disease could be treated in the womb by the stem cell therapy discovered by scientists.

Osteogenesis Imperfecta (OI) is the most common disease causing fractures in childhood, some can even occur in the womb. Experts hope that the discovery will lead the way to similar procedures to remedy this problem in babies.

Collagen is one of the main building blocks for bone, and in OI, it fails to develop properly. Suffers can be left with multiple fractures due to stunted growth and weak bones. By the time they are teenagers, about 50 percent of people suffering from OI find that they have impaired hearing.

Researchers believe the findings could lead to the development of treatments for other diseases including muscular dystrophy. Only one in 10,000 people have OI, so the potential for treating other diseases as well is enticing.

A 14-day-old mouse with OI was given a stem cell transplant by a team at Imperial College London. The cells were derived from fetal blood. Compared to the untreated group of mice, the study revealed that the treated mice sustained a two thirds reduction in long bone fractures.

Another contrast was that the treated mice also developed longer, thicker, and stronger bones.

OI sufferers had fractures that eventually healed but they were left with deformities said Professor Nicholas Fisk who led the study.

“It will help us to understand what it is that leads to such a marked effect after a single transplant of stem cells, so that this can be harnessed to improve the results of stem cell therapy in repairing adult tissues and degenerative conditions,” he said.

“Our work suggests that, in the future, it could be possible to take stem cells from an unborn baby carrying the abnormal OI gene, manipulate them to correct the errant gene, and then put them back into the fetus to allow it to develop properly.”

“We only need to collect 100 or 200 microlitres of blood from the fetus, which is a tiny amount, less than a fifth of a milliliter of blood. From this tiny sample we can grow all that we need to provide the potential treatment.”

“However, with further work we should be able to gain the stem cells we need from amniotic fluid or the placenta; thereby removing any potential risk of drawing fetal blood.”

The two thirds reduction was called “extraordinary” by Professor Fisk, but he said it was not a cure. 60 percent of all the mice still had some sort of fracture, and baby mice still had an average of one fracture each.

Dr. Yolande Harley, of charity Action Medical Research, which funded the project, said: “Professor Fisk’s work is a real breakthrough. It suggests that if stem cells could be successfully transplanted before a baby with OI is even born, it could mean a significant improvement in the child’s health and quality of life.”

“This is a tremendous piece of work that could have implications for many more diseases and conditions.”

Heart Failure Recovery Boosted by Stem Cells

The administration of adult bone marrow stem cells (BMC) and mesenchymal stems cells (MSC) can aid in the recovery of myocardial infarction (MI) – commonly known as heart attack – and consequently increase survival rates according to a study in the Clinical and Experimental Pharmacology and Physiology published by Wiley-Blackwell.

The study is designed to evaluate the impact of systemic delivery of BMC and MSC on spontaneously hypertensive rats induced with MI.

Dr. Nardi, the lead author of the study called,

Stem Cell Heart Trial Receives Approval

Millions of heart attack patients could have their chances of survival boosted and quality of life improved when British surgeons begin their ground-breaking research next month.

During bypass operations, stem cells will be injected into the hearts of patients. The procedures will be carried out by a team at Bristol University.

Earlier this week, The Human Tissue Authority gave Raimondo Ascione, the surgeon leading the research, approval to carry out the trial.

This will be the first large-scale trial comparing patients given the treatment with those given placebo injections, and previous smaller studies have already provided hope that this approach could provide a breakthrough.

Usually because the arteries supplying the heart with blood become blocked with fatty deposits, the heart muscle is starved of oxygen and a heart attack can take place.

Scar tissue can be left behind that no longer contributes to pumping the blood around the body after a bypass operation which is designed to restore the blood supply.

The new study will test the effectiveness of stem cell injections in repairing these scars in patients who have had acute large heart attacks – in which the scarring penetrates more than halfway through the thickness of the heart wall.

Mr. Ascione said yesterday: “We expect that after six months we will have been able to reduce or even make the scars disappear completely.

Dying Legs Treated with Human Stem Cells

With the hope of growing small blood vessels and restoring circulation in the legs, two patients were the first to be treated by transplanting a purified form of the subjects’ own adult stem cells into the leg muscles. Both patients suffered from severely blocked arteries and faced possible leg amputations. This first U.S. trial of the technique that has worked on laboratory animals was conducted by Northwestern University Feinberg School of Medicine.

“They’re at the end of the therapeutic road and they’re ultimately facing potential amputation,” said Douglas Losordo, M.D., the Eileen M. Foell Professor of Heart Research and principal national investigator for the study. “This is hopefully a way to help them avoid that.”

Losordo is director of the university’s Feinberg Cardiovascular Research Institute and director of cardiovascular regenerative medicine at Northwestern Memorial Hospital.

“The stem cells themselves can assemble into blood vessels,” Losordo said. “They can also secrete growth factors that stimulate and recruit other stem cells to come into the tissue and help with the repair. It’s an amazing biology we’re trying to leverage in these folks.”

The approach has proven to be effective in mice and rats during pre-clinical studies where stem cells were transplanted into the limbs of the animals.

“Based on that, we think it has a good chance of helping humans,” Losordo noted.

“This is a dreadful disease in which the profession has failed to offer much in the way of relief for these patients,” Losordo said. “We’re hoping this will have some impact.”

The trial is being conducted at 20 different sites nationally. The first two patients received their transplants at Northwestern Memorial Hospital.

Wounds that don’t heal, the breakdown of tissue, and gangrene can be the result of severely blocked arteries in the leg and sharply diminished blood flow. More than 100,000 limbs are amputated in the United States due to the painful condition call critical limb ischemia (CLI).

Affecting 1.4 million people, the emerging health problem is serious. By the time they reach the age of 70, and estimated 15 percent of the population will suffer from this disease.

Patients who have exhausted all other medical options including angioplasty, stents and bypass surgery to repair blocked circulation in their legs were the target of the Northwestern-led phase I/IIa study, which will include 75 people with CLI around the country.

Affecting about 10 million people in the United States, critical limb ischemia is the result of advanced peripheral artery disease. In peripheral artery disease, people develop blockages in their arteries and vessels that slow or stop the blood flow to their legs.

The condition is called CLI when they have wounds on their legs or feet that will not heal and pain at rest in their lower legs. If left untreated, CLI can result in a patient having toes, a foot or even a leg amputated.

People begin to experience pain when they walk, then when just sitting, as CLI progresses. Since blood flow decreases when people lie down, the pain is the worst at night. In order to lessen the pain and aid in blood flow, some even sleep in chairs.

“Peripheral artery disease is a big health problem,” Losordo said. “There is an emerging awareness of this disease on public health.”

The risk of developing the condition is elevated by high blood pressure, diabetes, high cholesterol and smoking.

However, Losordo points out that, “some people don’t smoke, have diabetes or high blood pressure and can still have blocked arteries in their legs.”
Losordo uses the subject’s own purified stem cells for the randomized, double blind, placebo-controlled trial. CD34+ stem cell from bone marrow are first released into the blood stream by a stem cell stimulating drug. The patient takes this drug for five days prior to the stem cell extraction. Then, the CD34+ enriched blood is obtained by way of an intravenous line that is inserted into a subject’s vein to collect blood through a machine that removes a population of blood cells. Losordo further selects and enriches the cells to select only CD34+ cells.