Stem cells in capsules

In a first of its kind study, researchers at Johns Hopkins Medicine have developed a new technique that transports therapeutic stem cells in a multilayer microcapsule that not only protects the cells from being attacked by the body's immune system but also enables them to be seen on x-ray.

Using microcapsules, dubbed XCaps, that are visible using x-ray imaging techniques, the researchers were able to track the delivery, survival, and function of donor stem cells used to treat cardiovascular disease in rabbits

“In acute ischemia, you don't have the luxury of taking stem cells from the body and waiting two to three weeks to culture and expand them in the laboratory,” says Dara Kraitchman, VMD, PhD, an associate professor of radiology at The Johns Hopkins University School of Medicine in Baltimore, United States. “Ideally, we'd like to be able to take donor cells off the shelf, make them x-ray visible, protect them from the immune system, and deliver them precisely where we want them to be.”

The researchers created the XCaps by coating donor stem cells with layers of alginate, a compound that provokes little immune response; barium, a contrast agent that makes the microcapsule x-ray visible; and poly-L-lysine, which holds the microcapsule together. The outer coating is made up of another layer of alginate.

The researchers replicated the effects of severe peripheral arterial disease in 13 female rabbits by inserting a platinum coil in the artery supplying blood to the hind limbs of the animals. One day later, the female rabbits were randomly assigned to receive an injection of XCaps created from the stem cells of male rabbits, XCaps without stem cells, stem cells alone, or a sham injection. XCaps were visible on x-ray both immediately after injection and at two weeks, allowing the researchers to monitor the delivery and disposition of the XCaps.

“The nice thing about XCaps is that you can see each individual capsule very clearly on x-ray,” says Dr Kenyatta Cosby, a postdoctoral fellow at Johns Hopkins. “We also observed no accumulation of fibrous material around the capsules, which suggests a minimal immune response.” ”Since XCaps can be made using FDA-approved clinical-grade compounds, they represent the first potentially biocompatible therapy that will enable xray visualisation of stem cells to assist in targeting cellular therapeutics,” Kraitchman said.

Glutamate transmitter traced

A newly established research collaboration between Karolinska Institutet and AstraZeneca has for the first time created the conditions to study one of the brain’s most important neurotransmission systems – the glutamate system.

The neurotransmitter glutamate is involved in virtually all brain functions. But even though researchers’ PET cameras can produce images of other important neurotransmission systems, such as the dopamine and serotonin systems, until now it has not been possible to capture images of the glutamate system. This is because there has not been any suitable tracer that can bind specifically to the receptors in the glutamate system.

The researchers have now developed a tracer, which makes it possible for the first time to study the glutamate system. “The glutamate system is an area of keen interest for research, especially for gaining an understanding of neuropsychiatric disorders,” said Professor Lars Farde at Karolinska Institutet.

“All anti-psychotic medicines currently available on the market work via the dopamine system, for example. However, it may well turn out that glutamate receptors are even better drug targets.”

New TB test

A new test for diagnosing TB offers a quick and simple alternative to existing threeday methods, according to research published 1 June in the journal Clinical Infectious Diseases.

The study shows that the test, which involves taking three sputum samples from a patient over the course of one day, is just as effective as other more invasive and complicated testing methods, which take three days. For the new test, patients use a nebuliser to inhale salty water, or hypertonic saline, for 20 minutes.

This enables them to produce sputum samples from deep inside the lungs. The samples can then be analysed for traces of mycobacterium tuberculosis, the bacterium which causes most cases of TB.

The new research, which was carried out by researchers from UK-based Imperial College London and Northwick Park Hospital, showed that the new test is just as effective, if not more so, than existing methods for diagnosing TB.

Bleeding lungs

Researchers at Queen Mary University London and the University of Leicester and have announced (1 June) a potential breakthrough in the treatment of a rare but devastating medical condition that can affect children and young people. In a world first, the clinicians and scientists from the two universities have already treated one patient with promising results.

Their preliminary data are published as a letter in the New England Journal of Medicine. This is the first time research into a condition known as “idiopathic pulmonary haemosiderosis” has investigated the role of ‘oxidative stress’ and it is also the first time treatment has been carried out based on the research.

Jonathan Grigg, Professor of Paediatric Respiratory and Environmental Medicine at Queen Mary University London, said: “Idiopathic pulmonary haemosiderosis is a rare disease, the cause of which is unknown. “Affected patients have episodes of bleeding in the lungs, which often need hospital admissions, and in some cases it can be life threatening.

This is normally combated by the use of continuous oral steroids (which can have major side effects). “In a child local to Leicester, we were able to show, for the first time, that there was high levels of oxidative stress in the lungs. In addition, we treated the increased oxidative stress by using an antioxidant, N-acetyl cysteine, which has no side effects. Since she has been on this treatment she has had no lung bleeds, and the steroid dose has been significantly reduced.”

Stem cells produce insulin

In a fundamental discovery that someday may help cure type 1 diabetes by allowing people to grow their own insulin-producing cells for a damaged or defective pancreas, medical researchers in the United States have reported that they have engineered adult stem cells derived from human umbilical cord blood to produce insulin.

The researchers announced their laboratory finding, which caps nearly four years of research, in the June 2007 issue of the medical journal Cell Proliferation. Their paper calls it “the first demonstration that human umbilical cord blood-derived stem cells can be engineered” to synthesize insulin.

“This discovery tells us that we have the potential to produce insulin from adult stem cells to help people with diabetes,” said Dr Randall J Urban, senior author of the paper, professor and chair of internal medicine at the University of Texas Medical Branch (UTMB) at Galveston and director of UTMB’s Nelda C and Lutcher H J Stark Diabetes Center.

Stressing that the reported discovery is extremely basic research, Urban cautioned: “It doesn’t prove that we’re going to be able to do this in people – it’s just the first step up the rung of the ladder.” The lead author of the paper, UTMB professor of internal medicine/ endocrinology Larry Denner, said that by working with adult stem cells rather than embryonic stem cells, doctors practicing so-called regenerative medicine eventually might be able to extract stem cells from an individual’s blood, then grow them in the laboratory to large numbers and tweak them so that they are directed to create a needed organ.

In this way, he said, physicians might avoid the usual pitfall involved in transplanting cells or organs from other people – organ rejection, which requires organ recipients to take immune-suppressing drugs for the rest of their lives.

Huge numbers of stem cells are thought to be required to create new organs. Researchers might remove thousands of donor cells from an individual and grow them in the laboratory into billions of cells, Denner explained. Then, for a person with type 1 diabetes, researchers might engineer these cells to become islets of Langerhans, the cellular masses that produce the hormone insulin, which allows the body to utilise sugar, synthesize proteins and store neutral fats, or lipids. “But we’re a long way from that,” Denner warned.

Denner said this research, which reflects a fruitful collaboration with coauthors Drs Colin McGuckin and Nico Forraz at the University of Newcastle Upon Tyne in the United Kingdom, used human umbilical cord blood because it is an especially rich source of fresh adult stem cells and is easily available from donors undergoing Caesarian section deliveries in UTMB hospitals.

“However,” he added, “embryonic stem cell research was absolutely necessary to teach us how to do this.” Embryonic stem cells have been engineered to produce cardiac, neural, blood, lung and liver progenitor cells that perform many of the functions needed to help replace cells and tissues injured by many diseases, the paper notes. Among the insights into cell and tissue engineering gained from work with embryonic stem cells, it adds, are those “relevant to the engineering of functional equivalents of pancreatic, islet-like, glucose- responsive, insulinproducing cells to treat diabetes.”

The researchers said they tested adult stem cells in the laboratory to ensure that they were predisposed to divide. Then they used a previously successful method in which complex signals produced by the embryonic mouse pancreas were used to direct adult stem cells to begin developing, or “differentiating”, into islet-like cells.

As they grew these adult stem cells in the laboratory, the researchers conducted other tests in which the cells to be engineered showed evidence of a characteristic, or marker, known as SSEA-4 that was previously thought to exist only in embryonic cells.

They also found that, just as embryonic cells have been shown to do, these adult stem cells produced both Cpeptide, a part of the insulin precursor protein, and insulin itself. Confirming the presence of the C-peptide was especially crucial, the researchers suggested, because although insulin is often found in the growth media with which the cells are nurtured and is often taken up by such cells, the presence of the C-peptide proves that at least some of the insulin was produced, or synthesized, by the engine.

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