Tissue engineering, already on a roll at Wake Forest University’s Institute for Regenerative Medicine, is adding heart valves to the list of body parts (bladders and blood vessels are already available) likely to become staples of regenerative medicine. One angineered heart valve was grown in the lab from a type of stem cell found in amniotic fluid, which shows signs of the pluripotency found in embryonic stem cells, without the latter’s physical and ethical side-effects.

A clinical trial of a fetal stem cell therapy for Batten disease (with potential for other neurodegenrative disorders) is underway. Early results were promising, but the jury will remain out for a while yet.

A combination of tissue engineering and genetic engineering has produced supermice with better, stronger muscles and greater physical endurance than normal mice. It could be used one day to treat patients with muscle-wasting diseases – and probably sooner (and illicitly) by aspiring sports superstars.

Another combination – angioplasty and stem cell therapy – is to be tried for improving both the immediate and long-term outcomes of acute heart attack.

Human clinical trials are planned following a successful stem cell treatment of diabetic, kidney-damaged mice.

Implanted chips to help restore vision to the blind have shown some success and are stunning technology, but the ultimate therapy would be the restoration of natural sight by repairing as opposed to bypassing damaged eyes. A major step in this direction has been successfully taken in blind mice.

Institute for Regenerative Medicine

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Wake Forest University’s Dr. Anthony Atala, a urologist famous for implanting the first bioengineered replacement organs – bladders – into seven children with spina bifida, appears to be having little trouble raising money. It amounts to tens of millions of dollars from the university, government agencies, biotech and pharmaceutical companies, and private investors for his Institute for Regenerative Medicine and for Tengion, a spinoff for-profit company aiming to commercialize the (currently 20 or so) tissue-engineered body parts the Institute is working on.

Last year, Institute researchers turned stem cells from circumcised foreskins into bone, fat, and muscle. They are currently trying to manufacture blood vessel shafts that could be implanted in the arms of kidney patients on dialysis, and to tissue-engineer replacement patches of muscle. They envision one day tackling the production of whole limbs.

Regenerative Therapy for Newborn Hearts

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University of Zurich scientists have grown human heart valves using fetal stem cells from amniotic fluid, reports Lindsay Tanner for the Associated Press. They hope to create valves more durable and effective than artificial or cadaver valves for unborn babies with heart defects, so the valves are ready to implant after birth.

Japanese researchers say they have also grown new heart valves, in rabbits, using cells from the animals’ own tissue.

Both methods avoid the controversy over embryonic stem cells, and have advatages over existing options, artifical valves and cadaver valves. Artificial valves are prone to blood clots and patients must take anti-clotting drugs for life. Valves from human cadavers or animals can deteriorate, requiring repeated open-heart surgeries to replace them. That’s especially true in children, because these valves don’t grow along with the body.

Pluripotency in Amniotic Fluid Cells

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A team led by Dr. Anthony Atala, the Wake Forest University scientist who successfully implanted tissue-engineered bladders in children and teenagers with spina bifida, has discovered a new class of stem cells in amniotic fluid, the liquid that surrounds embryos and fetuses in women’s wombs, as well as in the placenta, the blood-rich organ that nourishes fetuses in the womb.

Amniotic fluid is routinely extracted during pre-natal tests and the placenta is usually discarded after birth. This means they could be a non-controversial source of stem cells for research and therapeutic purposes. However, Atala notes that the cells are different from embryonic stem cells, though they may play a role in embryonic growth and development. He also says that they have different molecular fingerprints than stem cells found previously in animal and human amniotic fluid by other researchers.

His team’s cells are apparently more pluripotent and have been turned into muscle, bone, fat, blood vessel, nerve, and liver cells without the side effect common to embryonic stem cells of growing out of control and producing tumors.

Brain cells cultured from amniotic stem cells have been implanted in brain-injured mice, where they grew and filled in a damaged portion of the mice brains. Liver and bone cells produced from the stem cell supply also multiplied when inserted into mice.

Nevertheless, Dr. Atala caution that it is early days and there remains much to be understood, and some scientists not connected with his work remain sceptical about the research claims.

Nerve Stem Cell Transplant

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Last November a 6-year-old child with Batten disease, a rare but fatal neurodegenerative disorder, became the first human to receive injections of neural stem cells directly into the brain. The child is one of six in a phase I (safety) trial of a therapy jointly developed by the Oregon Health Sciences University and Stem Cells, Inc., whose scientists have identified a strain of stem cells that produce the enzyme whose absence causes neuronal ceroid lipofuscinosis (NCL) – the key factor in Batten disease.

The hope is that the injected stem cells will manufacture the enzyme and halt the disease.

The researchers used neural stem cells obtained from aborted fetuses rather than embryonic stem cells, because fetal neural stem cells are unlikely to develop into anything other than cell varieties already found in the brain. Embryonic stem cells would have the potential to grow into bone, hair, or eye tissue, to disastrous effect, writes Kaspar Mossman in Scientific American .

Stem cells can be injected beyond the blood-brain barrier, which blocks many drugs used in traditional therapies. And they can survive indefinitely, migrating to regions in the brain where they are needed before developing into their final form.

In the future, instead of transplantations of cells derived from fetuses, the cells will be made in the laboratory. Stem Cells Inc. purifies fetal cells, multiplies them a thousandfold, and freezes them in “cell banks” for individual patient use. The company “expects eventually to profit as the pharmaceutical industry does, by selling a product – ‘stem cells in a bottle,’” writes Mossman.

Twenty-eight days after the surgery, the child, who suffered seizures before, had none, and spoke words the parents had “not heard in a long time.” But this was only a safety trial, and the researchers are being very cautious about claiming therapeutic effects at this early stage.

The work could lead to similar treatments for Huntington’s, Alzheimer’s and Parkinson’s diseases.

Better Muscle

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Harvard researchers have genetically re-engineered muscle in mice to produce an abundance of a rare type of muscle fiber known as IIX, which is naturally present but only in small amounts. “These IIX-rich animals,” reports the BBC News, “were quite the little athletes,… able to run an average of 33 minutes before pooping out, compared with 26 minutes for their [untreated mice] counterparts.”

The method should enable deeper study of IIX fibers and could be used to treat muscle-wasting diseases such as muscular dystrophy.

Angioplasty + Stem Cells for Broken Hearts

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A 100-patient clinical trial getting under way at several hospitals in London will be the first to combine primary angioplasty with a bone marrow stem cell injection to try to combat the risk of death in both the immediate and long-term aftermath of a heart attack.

Heart attack patients brought to the hospitals for direct coronary intervention will be recruited for the study. 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.

Possible Cure for Diabetes

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Tulane University scientists have injected stem cells from human bone marrow to repair defective insulin-producing pancreatic cells in diabetic mice with high blood sugar and damaged kidneys. After three weeks, treated mice had higher levels of mouse insulin and lower blood sugar levels than untreated mice.

The injections also appeared to halt damaging changes taking place in the glomeruli, the bulb-like structures in the kidneys that filter the blood.

The team is planning to carry out trials in patients with diabetes and failing kidneys.

Blind Mice Vision Restored

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Retinal stem cells transplanted into mice with damaged cone and rod photoreceptor cells appear to have restored vision to the blind animals. Their pupils responded to light and there was activity in the optical nerve, showing signals were being sent to the brain. Nature called the achievement by scientists from University College London and Moorfields Eye Hospital “stunning,” according to the BBC News.

Similar attempts have failed in the past because the stem cells were not developed enough, so the scientists used cells from three to five-day-old mice – a stage when the retina is about to be formed, meaning that the cells are already programmed to develop into photoreceptors as opposed to any other type of adult cell.

To obtain human retinal stem cells at the same stage of development, however, would involve taking them from a foetus during the second trimester of pregnancy, which is clearly not an option. The researchers intend to genetically modify certain adult retinal cells – identified as having stem cell-like properties – to behave like the mouse retinal cells.

While it will be some time before a treatment emerges from this research, there is now at least reason to believe a treatment is possible.

 

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