Another therapy in human trials that regenerates diseased or damaged blood vessels could eventually put stent makers out of business. Bone marrow stem cell therapy is also going on clinical trial for patients who have suffered a recent (within five hours) heart attack.

Meanwhile embryonic stem cells continue to show their therapeutic potential with some success in animals aflicted with a Parkinson’s-like syndrome. But the therapy also caused brain tumors to develop. Similar experiments on spine-cord-injured animals have shown the benefit without the unwanted cancerous side effect.

Other relevant news:

• The possibility of therapeutic cloninghas been advanced by the discovery that clones can be produced from differentiated cells, not only from stem cells. 

   

• We wrote in the September issue about the likelhood of an artificial pancreasin five years. That was an external machine. Now there is a chance of tissue engineering a real pancreas from stem cells. 

   

• Through a successful study in mice, Howard Hughes Medical Institute researchers may have found a way to regenerate strong bone in osteoporosis patients. If it translates to humans, this proteomic therapy would have an enormous impact on lowering the cost and improving the quality of healthcare for the boomer population.

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“Like salamanders and other lower species, humans possess genes that direct the body to make new arms and legs after an injury. But in humans, the genes lie dormant, inactivated after evolution favored the swift patching of wounds through scarring over the slow regeneration of body parts,” writes Chicago Tribune science reporter Ronald Kotulak. He continues: “The discoverer of those genetic switches, Northwestern developmental biologist Hans-Georg Simon, and other researchers think they can find a way to turn on the dormant genes. A person who lost a leg might be able to generate a new one.” While no-one expects this to happen “any time soon,” says Kotulak, “there is increasing optimism that therapies can be developed in the next five to 10 years to prevent the formation of scars and to restore damaged or lost tissue from wounds, heart attacks, spinal cord injuries or Alzheimer’s disease.”

To that end, the US Defense Advanced Research Projects Agency (DARPA), is financing two teams in an approximately US$30 million four-year project to come up with “some sort of topical treatment that you could give a wounded soldier on the battlefield or shortly after and get them healing along a regenerative pathway,” as one researcher described it. One team will focus on ways to prevent scarring. The goal for the other team is to have a mouse regenerate a finger. Human babies have long been known to emerge from fetal surgery perfectly healed and without scars. The same genes (known as Tbx5 for arms and Tbx4 for legs) that regulate this in humans are also present in amphibian species such as salamanders, but in the case of humans and other mammals, the genes get turned off shortly before birth. The research project aims to find the regeneration switch and turn it back on.

They are not starting from scratch: Proteins have already been identified and are commercially available to help people regrow tendons after suffering rotator cuff and Achilles’ heel injuries; Vitamin A has been identified as a key ingredient in regenerative capacity; as we reported in March 2006, regenerated bladders have already made a successful appearance; and (again as we have previously reported, in November 2005) researchers at the University of Pennsylvania’s Wistar Institute have already induced regeneration of whole limbs and organs in a special research startin of mice, though they stumbled on the phenomenon and did not then understand the regenerative mechanism. Regeneration opens the door to “the next evolution of medical treatments,” according to what Kotulak describes as a “new: report, “2020: A New Vision–A Future for Regenerative Medicine,” which in fact was published in January 2005 by the US Department of Health and Human Services. That has to be one of the understatements of the century.

Adult Stem Cell Therapy Trial

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Researchers at the Mayo Clinic and Shands Hospital are collaborating on a 150-patient clinical trial to determine if adult stem cells can be used to alleviate angina, a leading symptom of cardiovascular disease, reports Urvaksh Karkaria in the Florida Times-Union. They will extract stem cells from the patients’ blood to stimulate the growth of new blood vessels in the heart muscle, increasing the flow of blood and thereby helping regenerate damaged heart tissue. The therapy has been proven safe in small phase I trials. The 12-month phase II study will be conducted at up to 20 hospitals across the US. Trial participants will be given medication to trigger the release of bone marrow stem cells into the blood stream. Blood will then be drawn and processed to isolate the stem cells, which will then be injected into the damaged areas of the heart. It may be at least a decade before such therapy is widely available, since there remain many uncertainties about the right stem cells to use, ways to harvest them, and coaxing them into becoming the right kind of tissue.

Tissue-engineered Arterial Repair

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Pervasis Therapeutics, a small Boston-area startup with impressive financial and scientific backers, hopes to complete phase 1 safety trials of a therapy to fix damaged or diseased arteries and veins “not with tools, but by wrapping them in a gelatinous sheath of living, healthy cells,” reports Stephen Heuser in the Boston Globe. The therapy, if successful, would challenge drugs and drug-eluting stents. A company co-founder described it as a “cellular Band-aid.” The product uses cells harvested from the smooth inner lining of a cadaver’s blood vessels, which are then lab-grown into a tiny sheet of living tissue which is then wrapped around the outside of the artery. The cells appear to to cause the artery to rebuild itself from the inside.

If successful in clinical trials, it would show that “you could get 95 percent of the functionality that you wish, without getting anywhere close to 100 percent of the structure,” a company official said. The company’s first trials involve kidney dialysis patients, whose blood vessels accrue serious scarring from repeated dialysis access. Future tests could include coronary bypass patients and trauma surgery patients. There remain many hurdles. Rejection of the foreign cells could be an issue, and live-cell products have a notoriously short shelf life. Pervasis claims a shelf life of up to two weeks, and its cells have not caused allergic reactions in animal trials on.

Stem Cells for Broken Hearts

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Up to 100 heart attack patients at London’s St. Barts Hospital are to be given injections of their own bone marrow stem cells within five hours of their attack, based on evidence that bone marrow stem cells can repair damaged heart muscle. The trial is the first to be funded by the UK Stem Cell Foundation. If successful, the therapy would help prevent subsequent heart failure, which is more of a threat than the initial attack itself. The trial will combine primary angioplasty with a stem cell injection. Following primary angioplasty, a stem cell sample will be taken from the patient’s own bone marrow. Once the cells have been prepared, patients will receive the sample into the previously blocked artery.

Stem Cell Therapy for Parkinson’s Is Half Way There

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“Nerve cells grown from human embryonic stem cells and injected into the brains of rats with a syndrome mimicking Parkinson’s disease significantly reduced the animals’ symptoms, but the treatment also caused tumors in the rodents’ brains,” reports Rick Weiss in the Washington Post. The study’s lead researcher said he suspected that with modest changes in technique, the risk of tumors might be eliminated or reduced, but much more basic research would have to be done before the therapy could be tried in humans. In the experiments, human embryonic stem cells were cultured in the lab to become neurons that produce the neurotransmitter dopamine — the type of cells that are lost in Parkinson’s disease. The cells were injected into the brains of rats that had been chemically damaged to mimic the damage caused by Parkinson’s. The new cells integrated into the animals’ brains and produced copious amounts of dopamine. As a result, the animals’ motor coordination improved almost to the point of being normal, writes Weiss, but on autopsy three months later multiple tumors were found in the brains, indicating that some of the injected cells had turned cancerous.

The results were similar to other experiments in which the stem cells were cultivated differently, producing less dopamine and fewer beneficial effects but still produced tumors. Biotech firm Geron, which hopes to obtain US Food and Drug Administration permission in 2007 to treat spinal-cord-injury patients with modified embryonic stem cells, said its cells have shown no sign of causing tumor growth in any of its animal studies. Geron cultivates its embryonic stem cells differently than others, he said, adding that no tumors have been seen in animals up to nine months after injections into the rodents’ injured spinal cords. Moreover, the cells survive and help the animals recover, in part by secreting special factors that spur new nerve growth around the injury.

Cloning Without Stem Cells

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The cloning by a multi-university research team of two mice pups from a kind of blood cell that cannot replicate suggests that adult stem cells may not be needed for successful animal cloning and indeed may not be as beneficial as differentiated cells, reports Anita Srikameswaran in the Pittsburgh Post-Gazette. “That’s good news for therapeutic cloning research because you can get differentiated cells in large quantity very easily,” one of the US researchers pointed out. However, the two cloned mouse pups died a few hours after birth. “Although the whole organism can be developed, it doesn’t mean it’s healthy,” the researcher said. “Most cloned animals are not really healthy.”

Human-Bovine Embryonic Stem Cells

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UK scientists have applied to the government Human Fertilisation and Embryology Authority for a three-year licence to create embryos by fusing human DNA with cow eggs, reports BBC News Medical correspondent Fergus Walsh. They would insert human DNA into a cow’s egg which has had its genetic material removed, and then create an embryo by the same technique that produced Dolly the Sheep. The resulting embryo would be 99.9% human; the only bovine element would be DNA outside the nucleus of the cell. It would, though, technically be a chimera – part-human, part-animal. Stem cells in the hybrid human-bovine embryos would be harvested after six days of development and used for stem cell research. The embryos would be destroyed.

The aim would be to extract stem cells from the embryo when it is six days old, before destroying it. A researcher noted that “The current state of the technology is such that literally hundreds of human ooctyes (eggs) from young women [would] be required to generate a single human embryonic stem cell line. Therefore we consider it more appropriate to use non-human oocytes from livestock as a surrogate. We feel that the development of disease-specific human embryonic stem cell lines from individuals suffering from genetic forms of neurodegenerative disorders will stimulate both basic research and the development of new medicines to treat these horrific brain diseases.” Critics say it is unethical and potentially dangerous.

Tissue-engineered Pancreas Possible

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Biotech company Novocell has developed a process to turn human embryonic stem cells into pancreatic cells that can produce insulin and other hormones, reports Andrew Pollack in the New York Times. It could, after several years more research, lead to a therapy for people with Type 1, or juvenile, diabetes. The work is a significant advance on earlier efforts to turn various types of human or animal stem cells into cells that produce insulin. One scientist told Pollack: “It provides some very strong evidence that it will be possible to make insulin-producing pancreatic beta cells from human E.S. cells in a culture dish,” and that Novocell had achieved an efficiency of cell conversion and insulin production “orders of magnitude higher than anything previously accomplished.”

Novocell’s insulin-producing cells were derived by adding and subtracting various growth factors to the embryonic stem cells in stages that mimicked the process that cells in an embryo go through to become a pancreatic cell. Animal tests could begin in 2008 and human clinical trials in 2009.

Regenerative Cure for Osteoporosis Possible

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Howard Hughes Medical Institute researchers have succeeded in massively increasing bone mass in mice by tweaking the structure of a protein called NFATc1 in the body. The modification is so minor they hope the side-effects will be minimal if the process is repeated in humans suffering from osteoporosis.

“The results were dramatic, yet the molecular alteration is very, very minimal,” a researcher told the BBC News. “If you could find a small molecule that would flip 10% of the existing NFATc1 into the active form you could favour the formation of osteoblasts and make stronger bones.” Osteoporosis has a major impact on healthcare costs and the quality of patients’ lives.